Variant 4-186191678-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_207352.4(CYP4V2):c.-146C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 715,622 control chromosomes in the GnomAD database, including 80,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13809 hom., cov: 33)

Exomes 𝑓: 0.48 ( 66754 hom. )

Consequence

CYP4V2
NM_207352.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.35

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 4-186191678-C-T is Benign according to our data. Variant chr4-186191678-C-T is described in ClinVar as [Benign]. Clinvar id is 348292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186191678-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4V2	NM_207352.4 linkuse as main transcript	c.-146C>T		5_prime_UTR_variant	1/11	ENST00000378802.5
CYP4V2	XM_005262935.5 linkuse as main transcript	c.-146C>T		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4V2	ENST00000378802.5 linkuse as main transcript	c.-146C>T		5_prime_UTR_variant	1/11	1	NM_207352.4	P1	Q6ZWL3-1

Frequencies

GnomAD3 genomes

AF:

0.415

AC:

62946

AN:

151580

Hom.:

13807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.361

Gnomad AMR

AF:

0.384

Gnomad ASJ

AF:

0.432

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.450

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.431

GnomAD4 exome

AF:

0.479

AC:

270197

AN:

563940

Hom.:

66754

Cov.:

AF XY:

0.481

AC XY:

131989

AN XY:

274614

show subpopulations

Gnomad4 AFR exome

AF:

0.291

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.447

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.402

Gnomad4 FIN exome

AF:

0.465

Gnomad4 NFE exome

AF:

0.498

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.415

AC:

62958

AN:

151682

Hom.:

13809

Cov.:

AF XY:

0.409

AC XY:

30349

AN XY:

74124

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.432

Gnomad4 EAS

AF:

0.294

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.450

Gnomad4 NFE

AF:

0.501

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.459

Hom.:

2047

Bravo

AF:

0.402

Asia WGS

AF:

0.345

AC:

1194

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bietti crystalline corneoretinal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Corneal dystrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

Cadd

Benign

0.26

Dann

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over