22-17739395-A-G

Variant names:

• chr22-17739395-A-G
• ENST00000342111.9:c.412T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The ENST00000342111.9(BID):​c.412T>C​(p.Ter138Argext*?) variant causes a stop lost change. The variant allele was found at a frequency of 0.000000687 in 1,456,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: BID ENST00000342111.9 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in ENST00000342111.9 Downstream stopcodon found after 167 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BID	NM_001196.4	c.317T>C	p.Val106Ala	missense_variant	Exon 4 of 6	ENST00000622694.5	NP_001187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BID	ENST00000622694.5	c.317T>C	p.Val106Ala	missense_variant	Exon 4 of 6	1	NM_001196.4	ENSP00000480414.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456296 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724340

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Benign	0.78
DEOGEN2	Benign	0.35	.;.;T;.;.;T;.;T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.62	T;.;T;.;T;.;.;.;.
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.7	.;.;L;.;.;L;.;L;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.3	D;.;.;.;D;D;D;D;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0060	D;.;.;.;D;D;D;D;.
Sift4G	Uncertain	0.010	D;D;D;D;D;D;D;D;D
Polyphen		0.99	D;.;D;.;.;D;.;D;.
Vest4		0.67
MutPred		0.83		.;.;Gain of disorder (P = 0.0286);.;.;Gain of disorder (P = 0.0286);.;Gain of disorder (P = 0.0286);.;
MVP		0.35
MPC		0.69
ClinPred		0.88	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-18222161;