rs13146272

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.775C>A(p.Gln259Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,612,180 control chromosomes in the GnomAD database, including 310,979 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28214 hom., cov: 32)

Exomes 𝑓: 0.62 ( 282765 hom. )

Consequence

CYP4V2
NM_207352.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.23

Publications

105 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=1.9090473E-6).

BP6

Variant 4-186199057-C-A is Benign according to our data. Variant chr4-186199057-C-A is described in ClinVar as Benign. ClinVar VariationId is 263297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CYP4V2	NM_207352.4 link	c.775C>A	p.Gln259Lys	missense_variant	Exon 6 of 11	ENST00000378802.5	NP_997235.3
CYP4V2	XM_005262935.5 link	c.775C>A	p.Gln259Lys	missense_variant	Exon 6 of 11		XP_005262992.1
CYP4V2	XM_047450077.1 link	c.379C>A	p.Gln127Lys	missense_variant	Exon 4 of 9		XP_047306033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5 link	c.775C>A	p.Gln259Lys	missense_variant	Exon 6 of 11	1	NM_207352.4	ENSP00000368079.4
CYP4V2	ENST00000507209.5 link	n.1616C>A		non_coding_transcript_exon_variant	Exon 2 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.606

AC:

92014

AN:

151902

Hom.:

28197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.610

Gnomad AMI

AF:

0.681

Gnomad AMR

AF:

0.489

Gnomad ASJ

AF:

0.510

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.606

Gnomad FIN

AF:

0.662

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.593

GnomAD2 exomes

AF:

0.573

AC:

144116

AN:

251344

AF XY:

0.583

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.373

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.664

Gnomad NFE exome

AF:

0.637

Gnomad OTH exome

AF:

0.567

GnomAD4 exome

AF:

0.618

AC:

902697

AN:

1460160

Hom.:

282765

Cov.:

AF XY:

0.619

AC XY:

449627

AN XY:

726452

show subpopulations

African (AFR)

AF:

0.603

AC:

20178

AN:

33450

American (AMR)

AF:

0.383

AC:

17141

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

13610

AN:

26124

East Asian (EAS)

AF:

0.388

AC:

15391

AN:

39672

South Asian (SAS)

AF:

0.604

AC:

52085

AN:

86216

European-Finnish (FIN)

AF:

0.666

AC:

35556

AN:

53388

Middle Eastern (MID)

AF:

0.545

AC:

3142

AN:

5766

European-Non Finnish (NFE)

AF:

0.639

AC:

709347

AN:

1110508

Other (OTH)

AF:

0.601

AC:

36247

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

17548

35095

52643

70190

87738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18576

37152

55728

74304

92880

<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:

0.606

AC:

92073

AN:

152020

Hom.:

28214

Cov.:

AF XY:

0.605

AC XY:

44982

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.610

AC:

25281

AN:

41462

American (AMR)

AF:

0.489

AC:

7465

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.510

AC:

1768

AN:

3468

East Asian (EAS)

AF:

0.416

AC:

2144

AN:

5158

South Asian (SAS)

AF:

0.606

AC:

2917

AN:

4816

European-Finnish (FIN)

AF:

0.662

AC:

6994

AN:

10568

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.640

AC:

43475

AN:

67964

Other (OTH)

AF:

0.595

AC:

1250

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1857

3713

5570

7426

9283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.614

Hom.:

132282

Bravo

AF:

0.584

TwinsUK

AF:

0.640

AC:

2373

ALSPAC

AF:

0.636

AC:

2451

ESP6500AA

AF:

0.624

AC:

2749

ESP6500EA

AF:

0.630

AC:

5422

ExAC

AF:

0.585

AC:

71038

Asia WGS

AF:

0.529

AC:

1842

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bietti crystalline corneoretinal dystrophy

Benign:3

Mar 06, 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

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29083408, 18349091, 21232005, 20124536, 19278955) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Corneal dystrophy

Benign:1

Mar 06, 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

0.066

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.0

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.050

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0000019

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.2

PhyloP100

2.2

PrimateAI

Benign

0.27

PROVEAN

Benign

2.0

REVEL

Benign

0.13

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.024

MPC

0.084

ClinPred

0.00089

GERP RS

0.98

Varity_R

0.13

gMVP

0.41

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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