rs199476199

Variant names:

• chr4-186205233-T-C
• rs199476199
• NM_207352.4:c.1021T>C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_207352.4(CYP4V2):​c.1021T>C​(p.Ser341Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP4V2 NM_207352.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.13

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969
• PP5: Variant 4-186205233-T-C is Pathogenic according to our data. Variant chr4-186205233-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 39249.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-186205233-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4V2	NM_207352.4	c.1021T>C	p.Ser341Pro	missense_variant	Exon 8 of 11	ENST00000378802.5	NP_997235.3
CYP4V2	XM_005262935.5	c.1021T>C	p.Ser341Pro	missense_variant	Exon 8 of 11		XP_005262992.1
CYP4V2	XM_047450077.1	c.625T>C	p.Ser209Pro	missense_variant	Exon 6 of 9		XP_047306033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4V2	ENST00000378802.5	c.1021T>C	p.Ser341Pro	missense_variant	Exon 8 of 11	1	NM_207352.4	ENSP00000368079.4
CYP4V2	ENST00000502665.1	n.256T>C		non_coding_transcript_exon_variant	Exon 2 of 5	1
CYP4V2	ENST00000507209.5	n.5719T>C		non_coding_transcript_exon_variant	Exon 3 of 6	1
CYP4V2	ENST00000513354.5	n.111T>C		non_coding_transcript_exon_variant	Exon 2 of 5	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Bietti crystalline corneoretinal dystrophy Pathogenic:1

Apr 12, 2012

GeneReviews

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.56
Sift	Benign	0.096	T
Sift4G	Benign	0.11	T
Polyphen		0.92	P
Vest4		0.86
MutPred		0.84		Loss of catalytic residue at S341 (P = 0.1968);
MVP		0.87
MPC		0.30
ClinPred		0.73	D
GERP RS		-0.85
Varity_R		0.97
gMVP		0.87

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

Other links and lift over

dbSNP: rs199476199; hg19: chr4-187126387;