rs119103285

Variant names:

• chr4-186192004-G-A
• rs119103285
• NM_207352.4:c.181G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2 PP2 PP3_Strong PP5

The NM_207352.4(CYP4V2):​c.181G>A​(p.Gly61Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. G61G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYP4V2 NM_207352.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 4.77
• Publications: 8 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: Likely_pathogenic. The variant received 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 24 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: -0.12103 (below the threshold of 3.09). Trascript score misZ: -0.14191 (below the threshold of 3.09). GenCC associations: The gene is linked to Bietti crystalline corneoretinal dystrophy.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.994
• PP5: Variant 4-186192004-G-A is Pathogenic according to our data. Variant chr4-186192004-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 2190.Status of the report is no_assertion_criteria_provided, 0 stars.

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.181G>A	p.Gly61Ser	missense	Exon 1 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.181G>A	p.Gly61Ser	missense	Exon 1 of 11	ENSP00000368079.4	Q6ZWL3-1
	CYP4V2	ENST00000905173.1		c.181G>A	p.Gly61Ser	missense	Exon 1 of 12	ENSP00000575232.1
	CYP4V2	ENST00000905174.1		c.181G>A	p.Gly61Ser	missense	Exon 1 of 11	ENSP00000575233.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000310 Hom.: 0

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
2	-	-	Bietti crystalline corneoretinal dystrophy (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.87	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		4.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Pathogenic	0.87
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.84
MutPred		0.97		Loss of sheet (P = 0.1907)
MVP		0.97
MPC		0.40
ClinPred		1.0	D
GERP RS		4.4
PromoterAI		0.0057	Neutral
Varity_R		0.96
gMVP		0.91
Mutation Taster		=19/81	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.28		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs119103285; hg19: chr4-187113158;