Variant 22-17750140-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001196.4(BID):c.-24C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

BID
NM_001196.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.74

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:

BID (HGNC:):

BID links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BID	NM_001196.4 linkuse as main transcript	c.-24C>T		5_prime_UTR_premature_start_codon_gain_variant	2/6	ENST00000622694.5	NP_001187.1	P55957-1A8ASI8B3KT21
BID	NM_001196.4 linkuse as main transcript	c.-24C>T		5_prime_UTR_variant	2/6	ENST00000622694.5	NP_001187.1	P55957-1A8ASI8B3KT21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BID	ENST00000622694.5 linkuse as main transcript	c.-24C>T		5_prime_UTR_premature_start_codon_gain_variant	2/6	1	NM_001196.4	ENSP00000480414.1		P55957-1
BID	ENST00000622694.5 linkuse as main transcript	c.-24C>T		5_prime_UTR_variant	2/6	1	NM_001196.4	ENSP00000480414.1		P55957-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247770

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460950

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726764

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000254

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.31

DANN

Uncertain

0.98

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00071

LIST_S2

Benign

0.51

M_CAP

Benign

0.0036

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.77

REVEL

Benign

0.030

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.0

Vest4

0.26

MVP

0.048

MPC

0.47

ClinPred

0.16

GERP RS

-4.6

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.23

Position offset: 34

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