22-17739485-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001196.4(BID):āc.227C>Gā(p.Ser76Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 34)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
BID
NM_001196.4 missense
NM_001196.4 missense
Scores
3
4
9
Clinical Significance
Conservation
PhyloP100: 3.55
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 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 | UniProt |
---|---|---|---|---|---|---|---|
BID | NM_001196.4 | c.227C>G | p.Ser76Cys | missense_variant | 4/6 | ENST00000622694.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BID | ENST00000622694.5 | c.227C>G | p.Ser76Cys | missense_variant | 4/6 | 1 | NM_001196.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
Cov.:
34
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249434Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135012
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459020Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 725924
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GnomAD4 genome ? Cov.: 34
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34
ExAC
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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 05, 2024 | The c.365C>G (p.S122C) alteration is located in exon 4 (coding exon 4) of the BID gene. This alteration results from a C to G substitution at nucleotide position 365, causing the serine (S) at amino acid position 122 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Vest4
MutPred
Gain of methylation at K109 (P = 0.036);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at