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GeneBe

22-17739395-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000342111.9(BID):c.412T>G(p.Ter138GlyextTer69) variant causes a stop lost change. The variant allele was found at a frequency of 0.00000746 in 1,608,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

BID
ENST00000342111.9 stop_lost

Scores

4
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.11
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.957

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIDNM_001196.4 linkuse as main transcriptc.317T>G p.Val106Gly missense_variant 4/6 ENST00000622694.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIDENST00000622694.5 linkuse as main transcriptc.317T>G p.Val106Gly missense_variant 4/61 NM_001196.4 P1P55957-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
34
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000283
AC:
7
AN:
246916
Hom.:
0
AF XY:
0.00000746
AC XY:
1
AN XY:
134014
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000273
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000889
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000755
AC:
11
AN:
1456296
Hom.:
0
Cov.:
32
AF XY:
0.00000414
AC XY:
3
AN XY:
724340
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
74370
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsFeb 22, 2023The c.455T>G (p.V152G) alteration is located in exon 4 (coding exon 4) of the BID gene. This alteration results from a T to G substitution at nucleotide position 455, causing the valine (V) at amino acid position 152 to be replaced by a glycine (G). 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
0.64
BayesDel_addAF
Uncertain
0.026
T
BayesDel_noAF
Uncertain
0.10
Cadd
Benign
22
Dann
Benign
0.69
Eigen
Benign
0.17
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.52
T;.;T;.;T;.;.;.;.
MetaRNN
Pathogenic
0.96
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.69
T
MutationTaster
Benign
1.0
D;D;D;D;D;N
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-6.0
D;.;.;.;D;D;D;D;.
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D;.;.;.;D;D;D;D;.
Sift4G
Uncertain
0.0030
D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;D;.;.;D;.;D;.
Vest4
0.64
MutPred
0.83
.;.;Gain of disorder (P = 0.0155);.;.;Gain of disorder (P = 0.0155);.;Gain of disorder (P = 0.0155);.;
MVP
0.31
MPC
0.78
ClinPred
0.57
D
GERP RS
5.7
Varity_R
0.89
gMVP
0.61

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.

Other links and lift over

dbSNP: rs748334233; hg19: chr22-18222161; API