NM_207352.4:c.810T>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_207352.4(CYP4V2):c.810T>G(p.Ala270Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 1,612,346 control chromosomes in the GnomAD database, including 333,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29568 hom., cov: 33)

Exomes 𝑓: 0.64 ( 304079 hom. )

Consequence

CYP4V2
NM_207352.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.399

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 4-186201165-T-G is Benign according to our data. Variant chr4-186201165-T-G is described in ClinVar as [Benign]. Clinvar id is 166976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186201165-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.399 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4V2	NM_207352.4 link	c.810T>G	p.Ala270Ala	synonymous_variant	Exon 7 of 11	ENST00000378802.5	NP_997235.3	Q6ZWL3-1
CYP4V2	XM_005262935.5 link	c.810T>G	p.Ala270Ala	synonymous_variant	Exon 7 of 11		XP_005262992.1
CYP4V2	XM_047450077.1 link	c.414T>G	p.Ala138Ala	synonymous_variant	Exon 5 of 9		XP_047306033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5 link	c.810T>G	p.Ala270Ala	synonymous_variant	Exon 7 of 11	1	NM_207352.4	ENSP00000368079.4		Q6ZWL3-1
CYP4V2	ENST00000507209.5 link	n.1651T>G		non_coding_transcript_exon_variant	Exon 3 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.619

AC:

94096

AN:

151934

Hom.:

29553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.607

Gnomad AMI

AF:

0.709

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.414

Gnomad SAS

AF:

0.612

Gnomad FIN

AF:

0.684

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.604

GnomAD3 exomes

AF:

0.588

AC:

147567

AN:

250876

Hom.:

45110

AF XY:

0.598

AC XY:

81141

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.528

Gnomad EAS exome

AF:

0.392

Gnomad SAS exome

AF:

0.616

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.658

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.641

AC:

935732

AN:

1460294

Hom.:

304079

Cov.:

AF XY:

0.641

AC XY:

465673

AN XY:

726494

show subpopulations

Gnomad4 AFR exome

AF:

0.606

Gnomad4 AMR exome

AF:

0.396

Gnomad4 ASJ exome

AF:

0.533

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.613

Gnomad4 FIN exome

AF:

0.685

Gnomad4 NFE exome

AF:

0.665

Gnomad4 OTH exome

AF:

0.620

GnomAD4 genome

AF:

0.619

AC:

94143

AN:

152052

Hom.:

29568

Cov.:

AF XY:

0.618

AC XY:

45918

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.607

Gnomad4 AMR

AF:

0.504

Gnomad4 ASJ

AF:

0.521

Gnomad4 EAS

AF:

0.414

Gnomad4 SAS

AF:

0.612

Gnomad4 FIN

AF:

0.684

Gnomad4 NFE

AF:

0.663

Gnomad4 OTH

AF:

0.606

Alfa

AF:

0.631

Hom.:

75432

Bravo

AF:

0.598

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 17, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

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

- -

Dec 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bietti crystalline corneoretinal dystrophy

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 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. -

Corneal dystrophy

Benign:1

Jan 12, 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

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.0

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over