dbSNP rs2072392: BID:p.Asp60Asp (chr22-17743846-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001196.4(BID):c.180T>C(p.Asp60Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,612,632 control chromosomes in the GnomAD database, including 844 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 0.040 ( 175 hom., cov: 32)

Exomes 𝑓: 0.026 ( 669 hom. )

Consequence

BID
NM_001196.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.23

Publications

15 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP7

Synonymous conserved (PhyloP=-2.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BID	NM_001196.4 link	c.180T>C	p.Asp60Asp	synonymous_variant	Exon 3 of 6	ENST00000622694.5	NP_001187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BID	ENST00000622694.5 link	c.180T>C	p.Asp60Asp	synonymous_variant	Exon 3 of 6	1	NM_001196.4	ENSP00000480414.1

Frequencies

GnomAD3 genomes

AF:

0.0402

AC:

6122

AN:

152180

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0823

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0259

Gnomad ASJ

AF:

0.0265

Gnomad EAS

AF:

0.0864

Gnomad SAS

AF:

0.00848

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0398

GnomAD2 exomes

AF:

0.0278

AC:

6908

AN:

248342

AF XY:

0.0265

show subpopulations

Gnomad AFR exome

AF:

0.0820

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0322

Gnomad EAS exome

AF:

0.0841

Gnomad FIN exome

AF:

0.00420

Gnomad NFE exome

AF:

0.0233

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.0259

AC:

37852

AN:

1460334

Hom.:

669

Cov.:

AF XY:

0.0254

AC XY:

18477

AN XY:

726474

show subpopulations

African (AFR)

AF:

0.0827

AC:

2768

AN:

33464

American (AMR)

AF:

0.0185

AC:

828

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0305

AC:

798

AN:

26128

East Asian (EAS)

AF:

0.0975

AC:

3871

AN:

39694

South Asian (SAS)

AF:

0.00906

AC:

781

AN:

86248

European-Finnish (FIN)

AF:

0.00510

AC:

267

AN:

52306

Middle Eastern (MID)

AF:

0.0297

AC:

169

AN:

5698

European-Non Finnish (NFE)

AF:

0.0239

AC:

26566

AN:

1111758

Other (OTH)

AF:

0.0299

AC:

1804

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

2258

4516

6775

9033

11291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1094

2188

3282

4376

5470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0403

AC:

6130

AN:

152298

Hom.:

175

Cov.:

AF XY:

0.0391

AC XY:

2915

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0822

AC:

3418

AN:

41560

American (AMR)

AF:

0.0258

AC:

395

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

AN:

3472

East Asian (EAS)

AF:

0.0868

AC:

450

AN:

5182

South Asian (SAS)

AF:

0.00849

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00301

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0235

AC:

1597

AN:

68016

Other (OTH)

AF:

0.0399

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

303

605

908

1210

1513

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0307

Hom.:

Bravo

AF:

0.0448

Asia WGS

AF:

0.0590

AC:

206

AN:

3478

EpiCase

AF:

0.0248

EpiControl

AF:

0.0270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.057

(source)

DANN

Benign

0.33

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over