4-186201150-C-T

Variant names:

• chr4-186201150-C-T
• rs3817184
• NM_207352.4:c.802-7C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207352.4(CYP4V2):​c.802-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,609,926 control chromosomes in the GnomAD database, including 119,475 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10016 hom., cov: 33)
  • Exomes 𝑓: 0.38 (109459 hom.)
• Consequence: CYP4V2 NM_207352.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001202
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0880
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-186201150-C-T is Benign according to our data. Variant chr4-186201150-C-T is described in ClinVar as [Benign]. Clinvar id is 166975.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4V2	NM_207352.4	c.802-7C>T		splice_region_variant, intron_variant	Intron 6 of 10	ENST00000378802.5	NP_997235.3
CYP4V2	XM_005262935.5	c.802-7C>T		splice_region_variant, intron_variant	Intron 6 of 10		XP_005262992.1
CYP4V2	XM_047450077.1	c.406-7C>T		splice_region_variant, intron_variant	Intron 4 of 8		XP_047306033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5	c.802-7C>T		splice_region_variant, intron_variant	Intron 6 of 10	1	NM_207352.4	ENSP00000368079.4
CYP4V2	ENST00000507209.5	n.1643-7C>T		splice_region_variant, intron_variant	Intron 2 of 5	1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54176 AN: 151946 Hom.: 10010 Cov.: 33

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.374

GnomAD2 exomes AF: 0.334 AC: 83499 AN: 250166 AF XY: 0.330

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.333

Gnomad FIN exome AF: 0.430

Gnomad NFE exome AF: 0.404

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.379 AC: 553203 AN: 1457862 Hom.: 109459 Cov.: 35 AF XY: 0.373 AC XY: 270226 AN XY: 725316

African (AFR) AF: 0.300 AC: 10016 AN: 33360

American (AMR) AF: 0.237 AC: 10551 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7498 AN: 26052

East Asian (EAS) AF: 0.329 AC: 13021 AN: 39534

South Asian (SAS) AF: 0.154 AC: 13266 AN: 85922

European-Finnish (FIN) AF: 0.433 AC: 23098 AN: 53352

Middle Eastern (MID) AF: 0.280 AC: 1612 AN: 5762

European-Non Finnish (NFE) AF: 0.408 AC: 452059 AN: 1109114

Other (OTH) AF: 0.367 AC: 22082 AN: 60232

GnomAD4 genome AF: 0.356 AC: 54200 AN: 152064 Hom.: 10016 Cov.: 33 AF XY: 0.352 AC XY: 26186 AN XY: 74310

African (AFR) AF: 0.302 AC: 12537 AN: 41500

American (AMR) AF: 0.303 AC: 4641 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3468

East Asian (EAS) AF: 0.354 AC: 1812 AN: 5120

South Asian (SAS) AF: 0.154 AC: 745 AN: 4822

European-Finnish (FIN) AF: 0.430 AC: 4536 AN: 10560

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.407 AC: 27672 AN: 67982

Other (OTH) AF: 0.377 AC: 797 AN: 2112

Alfa AF: 0.373 Hom.: 6575

Bravo AF: 0.347

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

-

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

- -

Bietti crystalline corneoretinal dystrophy Benign:2

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. -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		-0.088
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0
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: rs3817184; hg19: chr4-187122304; COSMIC: COSV66505327; COSMIC: COSV66505327;