Variant 1-46930214-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000310638.9(CYP4A11):c.1461C>T(p.Ile487=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00343 in 1,614,112 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 54 hom., cov: 30)

Exomes 𝑓: 0.0020 ( 72 hom. )

Consequence

CYP4A11
ENST00000310638.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.22

Variant links:

Genes affected

CYP4A11 (HGNC:2642): (cytochrome P450 family 4 subfamily A member 11) 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 and hydroxylates medium-chain fatty acids such as laurate and myristate. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

CYP4A11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-46930214-G-A is Benign according to our data. Variant chr1-46930214-G-A is described in ClinVar as [Benign]. Clinvar id is 774797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4A11	NM_000778.4 linkuse as main transcript	c.1461C>T	p.Ile487=	synonymous_variant	12/12	ENST00000310638.9	NP_000769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4A11	ENST00000310638.9 linkuse as main transcript	c.1461C>T	p.Ile487=	synonymous_variant	12/12	1	NM_000778.4	ENSP00000311095	P1	Q02928-1

Frequencies

GnomAD3 genomes

AF:

0.0171

AC:

2609

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00483

AC:

1214

AN:

251388

Hom.:

AF XY:

0.00351

AC XY:

477

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0621

Gnomad AMR exome

AF:

0.00341

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00200

AC:

2927

AN:

1461840

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1270

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0632

Gnomad4 AMR exome

AF:

0.00398

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000295

Gnomad4 OTH exome

AF:

0.00440

GnomAD4 genome

AF:

0.0172

AC:

2616

AN:

152272

Hom.:

Cov.:

AF XY:

0.0166

AC XY:

1237

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0595

Gnomad4 AMR

AF:

0.00470

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00490

Hom.:

Bravo

AF:

0.0196

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.8

DANN

Benign

0.66

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