chr4-186201201-T-C

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.846T>C(p.Cys282Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 1,614,064 control chromosomes in the GnomAD database, including 7,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 893 hom., cov: 31)

Exomes 𝑓: 0.074 ( 6822 hom. )

Consequence

CYP4V2
NM_207352.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.55

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=-0.88).

BP6

Variant 4-186201201-T-C is Benign according to our data. Variant chr4-186201201-T-C is described in ClinVar as [Benign]. Clinvar id is 166977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186201201-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.55 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4V2	NM_207352.4 link	c.846T>C	p.Cys282Cys	synonymous_variant	Exon 7 of 11	ENST00000378802.5	NP_997235.3	Q6ZWL3-1
CYP4V2	XM_005262935.5 link	c.846T>C	p.Cys282Cys	synonymous_variant	Exon 7 of 11		XP_005262992.1
CYP4V2	XM_047450077.1 link	c.450T>C	p.Cys150Cys	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.846T>C	p.Cys282Cys	synonymous_variant	Exon 7 of 11	1	NM_207352.4	ENSP00000368079.4		Q6ZWL3-1
CYP4V2	ENST00000507209.5 link	n.1687T>C		non_coding_transcript_exon_variant	Exon 3 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.0853

AC:

12975

AN:

152094

Hom.:

896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0629

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0942

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0529

Gnomad OTH

AF:

0.0974

GnomAD3 exomes

AF:

0.123

AC:

30982

AN:

251462

Hom.:

2992

AF XY:

0.120

AC XY:

16293

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0626

Gnomad AMR exome

AF:

0.236

Gnomad ASJ exome

AF:

0.132

Gnomad EAS exome

AF:

0.348

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0954

Gnomad NFE exome

AF:

0.0554

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.0742

AC:

108428

AN:

1461852

Hom.:

6822

Cov.:

AF XY:

0.0763

AC XY:

55467

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0646

Gnomad4 AMR exome

AF:

0.229

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.0900

Gnomad4 NFE exome

AF:

0.0491

Gnomad4 OTH exome

AF:

0.0924

GnomAD4 genome

AF:

0.0853

AC:

12983

AN:

152212

Hom.:

893

Cov.:

AF XY:

0.0907

AC XY:

6746

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0630

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.334

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.0942

Gnomad4 NFE

AF:

0.0529

Gnomad4 OTH

AF:

0.0959

Alfa

AF:

0.0654

Hom.:

672

Bravo

AF:

0.0926

Asia WGS

AF:

0.202

AC:

702

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

Apr 28, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

May 04, 2021

GeneDx

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

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. -

Bietti crystalline corneoretinal 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

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.17

DANN

Benign

0.26

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

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