NM_207352.4:c.14G>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_207352.4(CYP4V2):c.14G>T(p.Trp5Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,421,722 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. 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. W5S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CYP4V2
NM_207352.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

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: Uncertain_significance. The variant received 2 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=0.34235793).

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.14G>T	p.Trp5Leu	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.14G>T	p.Trp5Leu	missense	Exon 1 of 11	ENSP00000368079.4	Q6ZWL3-1
CYP4V2	ENST00000905173.1		c.14G>T	p.Trp5Leu	missense	Exon 1 of 12	ENSP00000575232.1
CYP4V2	ENST00000905174.1		c.14G>T	p.Trp5Leu	missense	Exon 1 of 11	ENSP00000575233.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1421722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704742

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32308

American (AMR)

AF:

0.00

AC:

AN:

41304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25362

East Asian (EAS)

AF:

0.00

AC:

AN:

37754

South Asian (SAS)

AF:

0.00

AC:

AN:

82132

European-Finnish (FIN)

AF:

0.0000242

AC:

AN:

41290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4808

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1097868

Other (OTH)

AF:

0.00

AC:

AN:

58896

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.054

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

1.6

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.080

REVEL

Benign

0.15

Sift

Benign

0.57

Sift4G

Pathogenic

0.0

Polyphen

0.0030

Vest4

0.32

MutPred

0.60

Loss of MoRF binding (P = 0.0016)

MVP

0.60

MPC

0.12

ClinPred

0.32

GERP RS

3.5

PromoterAI

-0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.095

gMVP

0.45

Mutation Taster

=95/5

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over