Variant chr22-17743838-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001196.4(BID):c.188G>C(p.Arg63Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BID
NM_001196.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.214

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008968115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BID	NM_001196.4 linkuse as main transcript	c.188G>C	p.Arg63Pro	missense_variant	3/6	ENST00000622694.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BID	ENST00000622694.5 linkuse as main transcript	c.188G>C	p.Arg63Pro	missense_variant	3/6	1	NM_001196.4	P1	P55957-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000388

AC:

AN:

244620

Hom.:

AF XY:

0.000262

AC XY:

AN XY:

133600

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.000302

Gnomad EAS exome

AF:

0.000277

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000862

Gnomad NFE exome

AF:

0.000392

Gnomad OTH exome

AF:

0.000841

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000685

AC:

100

AN:

1459384

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

726000

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00149

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000454

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00356

AC:

428

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2024

The c.326G>C (p.R109P) alteration is located in exon 3 (coding exon 3) of the BID gene. This alteration results from a G to C substitution at nucleotide position 326, causing the arginine (R) at amino acid position 109 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

0.0067

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.42

.;T;T;.;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.79

T;T;.;T;.;T

MetaRNN

Benign

0.0090

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

.;M;M;M;M;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-4.7

D;.;D;D;D;.

REVEL

Benign

0.24

Sift

Uncertain

0.012

D;.;D;D;D;.

Sift4G

Uncertain

0.0040

D;D;D;D;D;D

Polyphen

1.0

D;D;D;.;D;.

Vest4

0.57

MVP

0.36

MPC

0.84

ClinPred

0.063

GERP RS

-0.47

Varity_R

0.49

gMVP

0.49

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