rs762745532

Variant names:

• chr22-17750139-C-G
• rs762745532
• ENST00000317361.11:c.116G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-17750139-C-G
• chr22-17750139-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_197966.3(BID):​c.116G>C​(p.Arg39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign 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: 6.8e-7 (0 hom.)
• Consequence: BID NM_197966.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098566055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BID	NM_001196.4	c.-23G>C		5_prime_UTR_variant	Exon 2 of 6	ENST00000622694.5	NP_001187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BID	ENST00000622694.5	c.-23G>C		5_prime_UTR_variant	Exon 2 of 6	1	NM_001196.4	ENSP00000480414.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247796 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134682

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460968 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726780

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: 0.00

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
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.6
DANN	Uncertain	0.98
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.019
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		0.26	B
Vest4		0.46
MutPred		0.35		Loss of catalytic residue at R39 (P = 0.0137);
MVP		0.099
MPC		0.37
ClinPred		0.11	T
GERP RS		0.086
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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

Other links and lift over

dbSNP: rs762745532; hg19: chr22-18232905;