dbSNP rs11538: BID:p.Asn176Asn (chr22-17738065-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001196.4(BID):c.528T>C(p.Asn176Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,614,094 control chromosomes in the GnomAD database, including 20,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1523 hom., cov: 33)

Exomes 𝑓: 0.15 ( 19193 hom. )

Consequence

BID
NM_001196.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.506

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP7

Synonymous conserved (PhyloP=0.506 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BID	NM_001196.4 link	c.528T>C	p.Asn176Asn	synonymous_variant	Exon 5 of 6	ENST00000622694.5	NP_001187.1	P55957-1A8ASI8B3KT21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BID	ENST00000622694.5 link	c.528T>C	p.Asn176Asn	synonymous_variant	Exon 5 of 6	1	NM_001196.4	ENSP00000480414.1		P55957-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18769

AN:

152128

Hom.:

1523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0501

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0939

Gnomad EAS

AF:

0.00790

Gnomad SAS

AF:

0.0517

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.113

GnomAD3 exomes

AF:

0.128

AC:

32218

AN:

251474

Hom.:

2545

AF XY:

0.127

AC XY:

17202

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0476

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.00625

Gnomad SAS exome

AF:

0.0569

Gnomad FIN exome

AF:

0.189

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.130

GnomAD4 exome

AF:

0.155

AC:

225983

AN:

1461848

Hom.:

19193

Cov.:

AF XY:

0.152

AC XY:

110446

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0446

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.0996

Gnomad4 EAS exome

AF:

0.00542

Gnomad4 SAS exome

AF:

0.0592

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.173

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.123

AC:

18774

AN:

152246

Hom.:

1523

Cov.:

AF XY:

0.122

AC XY:

9045

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0500

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0939

Gnomad4 EAS

AF:

0.00811

Gnomad4 SAS

AF:

0.0522

Gnomad4 FIN

AF:

0.189

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.154

Hom.:

4149

Bravo

AF:

0.114

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

EpiCase

AF:

0.165

EpiControl

AF:

0.150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.3

DANN

Benign

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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