4-186191887-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_207352.4(CYP4V2):c.64C>T(p.Leu22Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,436,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L22V) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CYP4V2
NM_207352.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.996

Publications

45 publications found

Variant links:

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, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Illumina, G2P

CYP4V2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.08819917).

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.64C>T	p.Leu22Phe	missense	Exon 1 of 11	NP_997235.3	Q6ZWL3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP4V2	ENST00000378802.5	TSL:1 MANE Select	c.64C>T	p.Leu22Phe	missense	Exon 1 of 11	ENSP00000368079.4	Q6ZWL3-1
CYP4V2	ENST00000905173.1		c.64C>T	p.Leu22Phe	missense	Exon 1 of 12	ENSP00000575232.1
CYP4V2	ENST00000905174.1		c.64C>T	p.Leu22Phe	missense	Exon 1 of 11	ENSP00000575233.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

201924

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1436090

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33032

American (AMR)

AF:

0.00

AC:

AN:

42294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25738

East Asian (EAS)

AF:

0.00

AC:

AN:

38590

South Asian (SAS)

AF:

0.00

AC:

AN:

83538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5464

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1103610

Other (OTH)

AF:

0.0000168

AC:

AN:

59474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.5

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.17

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.91

REVEL

Benign

0.022

Sift

Benign

0.35

Sift4G

Benign

0.42

Polyphen

0.089

Vest4

0.036

MutPred

0.45

Gain of catalytic residue at L22 (P = 0.1033)

MVP

0.42

MPC

0.11

ClinPred

0.073

GERP RS

0.68

PromoterAI

-0.032

Neutral

(source)

Varity_R

0.055

gMVP

0.57

Mutation Taster

=59/41

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over