rs3736456

Variant names:

• chr4-186201201-T-C
• rs3736456
• NM_207352.4:c.846T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-186201201-T-C
• chr4-186201201-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.55
• Publications: 22 publications found

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: Illumina, G2P, ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 166977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207352.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4V2	NM_207352.4	MANE Select	c.846T>C	p.Cys282Cys	synonymous	Exon 7 of 11	NP_997235.3	Q6ZWL3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4V2	ENST00000378802.5	TSL:1 MANE Select	c.846T>C	p.Cys282Cys	synonymous	Exon 7 of 11	ENSP00000368079.4	Q6ZWL3-1
	CYP4V2	ENST00000507209.5	TSL:1	n.1687T>C		non_coding_transcript_exon	Exon 3 of 6
	CYP4V2	ENST00000905173.1		c.846T>C	p.Cys282Cys	synonymous	Exon 7 of 12	ENSP00000575232.1

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12975 AN: 152094 Hom.: 896 Cov.: 31

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

GnomAD2 exomes AF: 0.123 AC: 30982 AN: 251462 AF XY: 0.120

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 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.: 34 AF XY: 0.0763 AC XY: 55467 AN XY: 727234

African (AFR) AF: 0.0646 AC: 2162 AN: 33480

American (AMR) AF: 0.229 AC: 10227 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 3471 AN: 26134

East Asian (EAS) AF: 0.326 AC: 12958 AN: 39698

South Asian (SAS) AF: 0.160 AC: 13781 AN: 86250

European-Finnish (FIN) AF: 0.0900 AC: 4806 AN: 53418

Middle Eastern (MID) AF: 0.139 AC: 801 AN: 5768

European-Non Finnish (NFE) AF: 0.0491 AC: 54641 AN: 1111994

Other (OTH) AF: 0.0924 AC: 5581 AN: 60394

GnomAD4 genome AF: 0.0853 AC: 12983 AN: 152212 Hom.: 893 Cov.: 31 AF XY: 0.0907 AC XY: 6746 AN XY: 74406

African (AFR) AF: 0.0630 AC: 2616 AN: 41554

American (AMR) AF: 0.161 AC: 2457 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3466

East Asian (EAS) AF: 0.334 AC: 1718 AN: 5146

South Asian (SAS) AF: 0.167 AC: 805 AN: 4816

European-Finnish (FIN) AF: 0.0942 AC: 998 AN: 10598

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0529 AC: 3600 AN: 68022

Other (OTH) AF: 0.0959 AC: 203 AN: 2116

Alfa AF: 0.0677 Hom.: 1653

Bravo AF: 0.0926

Asia WGS AF: 0.202 AC: 702 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Bietti crystalline corneoretinal dystrophy (1)
-	-	1	Corneal dystrophy (1)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.17
DANN	Benign	0.26
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3736456; hg19: chr4-187122355; COSMIC: COSV66505958; COSMIC: COSV66505958;