Variant 22-17743998-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000622694.5(BID):c.28A>G(p.Ser10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,613,790 control chromosomes in the GnomAD database, including 687 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.036 ( 156 hom., cov: 32)

Exomes 𝑓: 0.021 ( 531 hom. )

Consequence

BID
ENST00000622694.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.685

Variant links:

Genes affected

BID (HGNC:1050): (BH3 interacting domain death agonist) This gene encodes a death agonist that heterodimerizes with either agonist BAX or antagonist BCL2, and thus regulate apoptosis. The encoded protein is a member of the BCL-2 family of cell death regulators. It is a mediator of mitochondrial damage induced by caspase-8 (CASP8); CASP8 cleaves this encoded protein, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. Multiple alternatively spliced transcript variants have been found. [provided by RefSeq, Aug 2020]

BID links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019285083).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BID	NM_001196.4 linkuse as main transcript	c.28A>G	p.Ser10Gly	missense_variant	3/6	ENST00000622694.5	NP_001187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BID	ENST00000622694.5 linkuse as main transcript	c.28A>G	p.Ser10Gly	missense_variant	3/6	1	NM_001196.4	ENSP00000480414	P1	P55957-1

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5491

AN:

152140

Hom.:

156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0784

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0234

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.0856

Gnomad SAS

AF:

0.00808

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0382

GnomAD3 exomes

AF:

0.0238

AC:

5968

AN:

251168

Hom.:

122

AF XY:

0.0224

AC XY:

3048

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.0789

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0217

Gnomad EAS exome

AF:

0.0840

Gnomad SAS exome

AF:

0.00892

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.0177

Gnomad OTH exome

AF:

0.0233

GnomAD4 exome

AF:

0.0212

AC:

30978

AN:

1461532

Hom.:

531

Cov.:

AF XY:

0.0208

AC XY:

15130

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.0786

Gnomad4 AMR exome

AF:

0.0145

Gnomad4 ASJ exome

AF:

0.0210

Gnomad4 EAS exome

AF:

0.0972

Gnomad4 SAS exome

AF:

0.00858

Gnomad4 FIN exome

AF:

0.00327

Gnomad4 NFE exome

AF:

0.0186

Gnomad4 OTH exome

AF:

0.0256

GnomAD4 genome

AF:

0.0361

AC:

5499

AN:

152258

Hom.:

156

Cov.:

AF XY:

0.0350

AC XY:

2603

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0784

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.0860

Gnomad4 SAS

AF:

0.00788

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0383

Alfa

AF:

0.0244

Hom.:

114

Bravo

AF:

0.0405

TwinsUK

AF:

0.0159

AC:

ALSPAC

AF:

0.0241

AC:

ESP6500AA

AF:

0.0783

AC:

345

ESP6500EA

AF:

0.0190

AC:

163

ExAC

AF:

0.0256

AC:

3109

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.0191

EpiControl

AF:

0.0205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.33

DANN

Benign

0.17

DEOGEN2

Benign

0.064

.;T;T;.;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00029

LIST_S2

Benign

0.12

T;T;.;T;.;T

MetaRNN

Benign

0.0019

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

.;N;N;N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

1.7

N;.;N;N;N;.

REVEL

Benign

0.014

Sift

Benign

1.0

T;.;T;T;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

B;B;B;.;B;.

Vest4

0.039

MPC

0.15

ClinPred

0.0010

GERP RS

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over