22-17743846-A-T

Variant names:

• chr22-17743846-A-T
• NM_001196.4:c.180T>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001196.4(BID):​c.180T>A​(p.Asp60Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,336 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BID NM_001196.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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 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, 0.989

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BID	NM_001196.4	c.180T>A	p.Asp60Glu	missense_variant	Exon 3 of 6	ENST00000622694.5	NP_001187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BID	ENST00000622694.5	c.180T>A	p.Asp60Glu	missense_variant	Exon 3 of 6	1	NM_001196.4	ENSP00000480414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460336 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726474

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	0.087
DANN	Uncertain	0.98
DEOGEN2	Benign	0.40	.;T;T;.;T;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.73	T;T;.;T;.;T
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	.;M;M;M;M;.
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.5	D;.;D;D;D;.
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;.;D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.96	P;D;D;.;D;.
Vest4		0.74
MutPred		0.90		.;Gain of phosphorylation at S64 (P = 0.1773);Gain of phosphorylation at S64 (P = 0.1773);Gain of phosphorylation at S64 (P = 0.1773);Gain of phosphorylation at S64 (P = 0.1773);Gain of phosphorylation at S64 (P = 0.1773);
MVP		0.36
MPC		0.42
ClinPred		0.97	D
GERP RS		-5.6
Varity_R		0.63
gMVP		0.56

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: chr22-18226612;