4-186201165-T-G

Variant names:

• chr4-186201165-T-G
• rs3736455
• NM_207352.4:c.810T>G

Variant summary

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

The ENST00000378802.5(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 (★★). Synonymous variant affecting the same amino acid position (i.e. A270A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.62 (29568 hom., cov: 33)
  • Exomes 𝑓: 0.64 (304079 hom.)
• Consequence: CYP4V2 ENST00000378802.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.399
• Publications: 47 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: Laboratory for Molecular Medicine, Illumina, Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 166976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378802.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4V2	NM_207352.4	MANE Select	c.810T>G	p.Ala270Ala	synonymous	Exon 7 of 11	NP_997235.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4V2	ENST00000378802.5	TSL:1 MANE Select	c.810T>G	p.Ala270Ala	synonymous	Exon 7 of 11	ENSP00000368079.4
	CYP4V2	ENST00000507209.5	TSL:1	n.1651T>G		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94096 AN: 151934 Hom.: 29553 Cov.: 33

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

GnomAD2 exomes AF: 0.588 AC: 147567 AN: 250876 AF XY: 0.598

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 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.: 50 AF XY: 0.641 AC XY: 465673 AN XY: 726494

African (AFR) AF: 0.606 AC: 20264 AN: 33428

American (AMR) AF: 0.396 AC: 17669 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 13898 AN: 26098

East Asian (EAS) AF: 0.386 AC: 15252 AN: 39552

South Asian (SAS) AF: 0.613 AC: 52817 AN: 86136

European-Finnish (FIN) AF: 0.685 AC: 36603 AN: 53398

Middle Eastern (MID) AF: 0.557 AC: 3211 AN: 5766

European-Non Finnish (NFE) AF: 0.665 AC: 738632 AN: 1110962

Other (OTH) AF: 0.620 AC: 37386 AN: 60334

GnomAD4 genome AF: 0.619 AC: 94143 AN: 152052 Hom.: 29568 Cov.: 33 AF XY: 0.618 AC XY: 45918 AN XY: 74308

African (AFR) AF: 0.607 AC: 25167 AN: 41492

American (AMR) AF: 0.504 AC: 7713 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1809 AN: 3472

East Asian (EAS) AF: 0.414 AC: 2114 AN: 5112

South Asian (SAS) AF: 0.612 AC: 2944 AN: 4814

European-Finnish (FIN) AF: 0.684 AC: 7234 AN: 10570

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45075 AN: 67986

Other (OTH) AF: 0.606 AC: 1277 AN: 2108

Alfa AF: 0.627 Hom.: 107695

Bravo AF: 0.598

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Bietti crystalline corneoretinal dystrophy (2)
-	-	1	Corneal dystrophy (1)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.45
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3736455; hg19: chr4-187122319; COSMIC: COSV66505335; COSMIC: COSV66505335;