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GeneBe

22-17743848-C-T

Variant summary

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

The NM_001196.4(BID):c.178G>A(p.Asp60Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BID
NM_001196.4 missense

Scores

5
5
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08
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, 0.978

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIDNM_001196.4 linkuse as main transcriptc.178G>A p.Asp60Asn missense_variant 3/6 ENST00000622694.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIDENST00000622694.5 linkuse as main transcriptc.178G>A p.Asp60Asn missense_variant 3/61 NM_001196.4 P1P55957-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 GeneticsMay 13, 2022The c.316G>A (p.D106N) alteration is located in exon 3 (coding exon 3) of the BID gene. This alteration results from a G to A substitution at nucleotide position 316, causing the aspartic acid (D) at amino acid position 106 to be replaced by an asparagine (N). 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
0.85
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.36
Cadd
Benign
22
Dann
Uncertain
1.0
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Benign
0.73
D
LIST_S2
Uncertain
0.87
D;D;.;D;.;D
M_CAP
Benign
0.049
D
MetaRNN
Pathogenic
0.98
D;D;D;D;D;D
MetaSVM
Benign
-0.61
T
MutationTaster
Benign
0.75
D;D;D;N;N;N
PrimateAI
Benign
0.47
T
PROVEAN
Pathogenic
-4.5
D;.;D;D;D;.
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
D;.;D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
D;D;D;.;D;.
Vest4
0.80
MutPred
0.91
.;Loss of phosphorylation at T59 (P = 0.0859);Loss of phosphorylation at T59 (P = 0.0859);Loss of phosphorylation at T59 (P = 0.0859);Loss of phosphorylation at T59 (P = 0.0859);Loss of phosphorylation at T59 (P = 0.0859);
MVP
0.55
MPC
0.68
ClinPred
0.99
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.70
gMVP
0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-18226614; API