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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4V2	NM_207352.4	MANE Select	c.802-7C>T		splice_region intron	N/A	NP_997235.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4V2	ENST00000378802.5	TSL:1 MANE Select	c.802-7C>T		splice_region intron	N/A	ENSP00000368079.4
	CYP4V2	ENST00000507209.5	TSL:1	n.1643-7C>T		splice_region intron	N/A

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

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;