rs1055138

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_207352.4(CYP4V2):c.64C>G(p.Leu22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,587,696 control chromosomes in the GnomAD database, including 186,194 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16288 hom., cov: 34)

Exomes 𝑓: 0.48 ( 169906 hom. )

Consequence

CYP4V2
NM_207352.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:15

Conservation

PhyloP100: -0.996

Publications

45 publications found

Variant links:

Genes affected

CYP4V2 (HGNC:23198): (cytochrome P450 family 4 subfamily V member 2) This gene encodes a member of the cytochrome P450 hemethiolate protein superfamily which are involved in oxidizing various substrates in the metabolic pathway. It is implicated in the metabolism of fatty acid precursors into n-3 polyunsaturated fatty acids. Mutations in this gene result in Bietti crystalline corneoretinal dystrophy. [provided by RefSeq, Jul 2008]

CYP4V2 Gene-Disease associations (from GenCC):

Bietti crystalline corneoretinal dystrophy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Illumina, Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

CYP4V2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 24 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: -0.12103 (below the threshold of 3.09). Trascript score misZ: -0.14191 (below the threshold of 3.09). GenCC associations: The gene is linked to Bietti crystalline corneoretinal dystrophy.

BP4

Computational evidence support a benign effect (MetaRNN=3.741501E-5).

BP6

Variant 4-186191887-C-G is Benign according to our data. Variant chr4-186191887-C-G is described in ClinVar as Benign. ClinVar VariationId is 39267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4V2	NM_207352.4 link	c.64C>G	p.Leu22Val	missense_variant	Exon 1 of 11	ENST00000378802.5	NP_997235.3	Q6ZWL3-1
CYP4V2	XM_005262935.5 link	c.64C>G	p.Leu22Val	missense_variant	Exon 1 of 11		XP_005262992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5 link	c.64C>G	p.Leu22Val	missense_variant	Exon 1 of 11	1	NM_207352.4	ENSP00000368079.4		Q6ZWL3-1

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69750

AN:

151928

Hom.:

16272

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.456

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.506

Gnomad OTH

AF:

0.460

GnomAD2 exomes

AF:

0.444

AC:

89568

AN:

201924

AF XY:

0.447

show subpopulations

Gnomad AFR exome

AF:

0.424

Gnomad AMR exome

AF:

0.387

Gnomad ASJ exome

AF:

0.466

Gnomad EAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.505

Gnomad OTH exome

AF:

0.467

GnomAD4 exome

AF:

0.484

AC:

694802

AN:

1435650

Hom.:

169906

Cov.:

AF XY:

0.482

AC XY:

343795

AN XY:

712832

show subpopulations

African (AFR)

AF:

0.425

AC:

14045

AN:

33024

American (AMR)

AF:

0.393

AC:

16606

AN:

42232

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

12040

AN:

25734

East Asian (EAS)

AF:

0.284

AC:

10951

AN:

38572

South Asian (SAS)

AF:

0.405

AC:

33857

AN:

83504

European-Finnish (FIN)

AF:

0.462

AC:

20446

AN:

44278

Middle Eastern (MID)

AF:

0.448

AC:

2449

AN:

5464

European-Non Finnish (NFE)

AF:

0.504

AC:

556326

AN:

1103380

Other (OTH)

AF:

0.472

AC:

28082

AN:

59462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

22614

45228

67843

90457

113071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16020

32040

48060

64080

80100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.459

AC:

69805

AN:

152046

Hom.:

16288

Cov.:

AF XY:

0.453

AC XY:

33718

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.427

AC:

17740

AN:

41512

American (AMR)

AF:

0.423

AC:

6465

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.456

AC:

1583

AN:

3470

East Asian (EAS)

AF:

0.282

AC:

1449

AN:

5130

South Asian (SAS)

AF:

0.398

AC:

1920

AN:

4828

European-Finnish (FIN)

AF:

0.460

AC:

4876

AN:

10598

Middle Eastern (MID)

AF:

0.428

AC:

125

AN:

292

European-Non Finnish (NFE)

AF:

0.506

AC:

34344

AN:

67908

Other (OTH)

AF:

0.463

AC:

977

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2000

4000

6001

8001

10001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.489

Hom.:

5601

Bravo

AF:

0.453

TwinsUK

AF:

0.489

AC:

1815

ALSPAC

AF:

0.503

AC:

1940

ESP6500AA

AF:

0.413

AC:

1786

ESP6500EA

AF:

0.489

AC:

4174

ExAC

AF:

0.421

AC:

49477

Asia WGS

AF:

0.354

AC:

1229

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bietti crystalline corneoretinal dystrophy

Pathogenic:1Benign:5

Nov 20, 2020

Molecular Genetics, Royal Melbourne Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Population allele frequency is 45% (101,504/227,310 alleles; gnomAD v2.0.2). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1 -

Apr 12, 2012

GeneReviews

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:curation

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 25, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Department of Ophthalmology and Visual Sciences Kyoto University

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Mar 14, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Corneal dystrophy

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.15

(source)

DANN

Benign

0.52

DEOGEN2

Benign

0.050

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0042

LIST_S2

Benign

0.12

MetaRNN

Benign

0.000037

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.90

PhyloP100

-1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.19

REVEL

Benign

0.027

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.014

MPC

0.11

ClinPred

0.0066

GERP RS

0.68

PromoterAI

-0.059

Neutral

(source)

Varity_R

0.039

gMVP

0.50

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over