dbSNP rs3215983: CYP4B1:p.Asp295GlyfsTer3 (chr1-46815074-GAT-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001099772.2(CYP4B1):c.884_885delAT(p.Asp295GlyfsTer3) variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.139 in 1,612,232 control chromosomes in the GnomAD database, including 16,629 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.12 ( 1398 hom., cov: 30)

Exomes 𝑓: 0.14 ( 15231 hom. )

Consequence

CYP4B1
NM_001099772.2 frameshift, splice_region

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.26

Variant links:

Genes affected

CYP4B1 (HGNC:2644): (cytochrome P450 family 4 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. In rodents, the homologous protein has been shown to metabolize certain carcinogens; however, the specific function of the human protein has not been determined. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

CYP4B1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-46815074-GAT-G is Benign according to our data. Variant chr1-46815074-GAT-G is described in ClinVar as [Benign]. Clinvar id is 402584.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-46815074-GAT-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4B1	NM_001099772.2 link	c.884_885delAT	p.Asp295GlyfsTer3	frameshift_variant, splice_region_variant	Exon 8 of 12	ENST00000371923.9	NP_001093242.1	P13584-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4B1	ENST00000371923.9 link	c.884_885delAT	p.Asp295GlyfsTer3	frameshift_variant, splice_region_variant	Exon 8 of 12	1	NM_001099772.2	ENSP00000360991.4		P13584-2

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18745

AN:

152030

Hom.:

1393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0520

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.143

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.134

GnomAD3 exomes

AF:

0.149

AC:

37317

AN:

250554

Hom.:

2955

AF XY:

0.147

AC XY:

19962

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.0525

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.242

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.142

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.140

AC:

204684

AN:

1460084

Hom.:

15231

AF XY:

0.140

AC XY:

102031

AN XY:

726420

show subpopulations

Gnomad4 AFR exome

AF:

0.0473

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.273

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.123

AC:

18756

AN:

152148

Hom.:

1398

Cov.:

AF XY:

0.126

AC XY:

9389

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0523

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.256

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.143

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.135

Hom.:

254

Bravo

AF:

0.122

Asia WGS

AF:

0.195

AC:

679

AN:

3478

EpiCase

AF:

0.140

EpiControl

AF:

0.135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 381/2178=17.49% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: 7

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