Genetic Variant NM_207352.4:c.25G>C (chr4-186191848-G-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong

The NM_207352.4(CYP4V2):c.25G>C(p.Val9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000982 in 1,425,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000098 ( 0 hom. )

Consequence

CYP4V2
NM_207352.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.19

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. 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=0.061001092).

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.25G>C	p.Val9Leu	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.25G>C	p.Val9Leu	missense	Exon 1 of 11	ENSP00000368079.4	Q6ZWL3-1
CYP4V2	ENST00000905173.1		c.25G>C	p.Val9Leu	missense	Exon 1 of 12	ENSP00000575232.1
CYP4V2	ENST00000905174.1		c.25G>C	p.Val9Leu	missense	Exon 1 of 11	ENSP00000575233.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000982

AC:

AN:

1425128

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

706836

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32448

American (AMR)

AF:

0.00

AC:

AN:

41452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25486

East Asian (EAS)

AF:

0.00

AC:

AN:

37684

South Asian (SAS)

AF:

0.00

AC:

AN:

82522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4982

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

1099722

Other (OTH)

AF:

0.00

AC:

AN:

59056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

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.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.045

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.069

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.46

PhyloP100

-2.2

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.20

REVEL

Benign

0.060

Sift

Benign

0.61

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.086

MutPred

0.50

Loss of loop (P = 0.0603)

MVP

0.22

MPC

0.066

ClinPred

0.038

GERP RS

-8.6

PromoterAI

-0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.038

gMVP

0.49

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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