rs181405

chr22-17750234-G-Achr22-17750234-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001196.4(BID):c.-58-60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,461,104 control chromosomes in the GnomAD database, including 162,393 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (13764 hom., cov: 34)
  • Exomes 𝑓: 0.47 (148629 hom.)
• Consequence: BID NM_001196.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BID	NM_001196.4	c.-58-60C>T		intron_variant		ENST00000622694.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BID	ENST00000622694.5	c.-58-60C>T		intron_variant		1	NM_001196.4	P1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59798 AN: 152122 Hom.: 13755 Cov.: 34

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.469 AC: 614260 AN: 1308864 Hom.: 148629 AF XY: 0.473 AC XY: 308711 AN XY: 652644

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.606

Gnomad4 ASJ exome AF: 0.487

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.582

Gnomad4 FIN exome AF: 0.402

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.393 AC: 59826 AN: 152240 Hom.: 13764 Cov.: 34 AF XY: 0.399 AC XY: 29680 AN XY: 74422

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.439

Alfa AF: 0.432 Hom.: 9788

Bravo AF: 0.394

Asia WGS AF: 0.635 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.9
Dann	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs181405; hg19: chr22-18233000; COSMIC: COSV58007123;