rs2072392

Positions:

• chr22-17743846-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001196.4(BID):​c.180T>C​(p.Asp60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,612,632 control chromosomes in the GnomAD database, including 844 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 0.040 (175 hom., cov: 32)
  • Exomes 𝑓: 0.026 (669 hom.)
• Consequence: BID NM_001196.4 synonymous
• 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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-2.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BID	NM_001196.4	c.180T>C	p.Asp60=	synonymous_variant	3/6	ENST00000622694.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BID	ENST00000622694.5	c.180T>C	p.Asp60=	synonymous_variant	3/6	1	NM_001196.4	P1

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6122 AN: 152180 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0398

GnomAD3 exomes AF: 0.0278 AC: 6908 AN: 248342 Hom.: 136 AF XY: 0.0265 AC XY: 3571 AN XY: 134928

Gnomad AFR exome AF: 0.0820

Gnomad AMR exome AF: 0.0170

Gnomad ASJ exome AF: 0.0322

Gnomad EAS exome AF: 0.0841

Gnomad SAS exome AF: 0.00944

Gnomad FIN exome AF: 0.00420

Gnomad NFE exome AF: 0.0233

Gnomad OTH exome AF: 0.0288

GnomAD4 exome AF: 0.0259 AC: 37852 AN: 1460334 Hom.: 669 Cov.: 32 AF XY: 0.0254 AC XY: 18477 AN XY: 726474

Gnomad4 AFR exome AF: 0.0827

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.0305

Gnomad4 EAS exome AF: 0.0975

Gnomad4 SAS exome AF: 0.00906

Gnomad4 FIN exome AF: 0.00510

Gnomad4 NFE exome AF: 0.0239

Gnomad4 OTH exome AF: 0.0299

GnomAD4 genome AF: 0.0403 AC: 6130 AN: 152298 Hom.: 175 Cov.: 32 AF XY: 0.0391 AC XY: 2915 AN XY: 74480

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.0868

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.00301

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0399

Alfa AF: 0.0283 Hom.: 51

Bravo AF: 0.0448

Asia WGS AF: 0.0590 AC: 206 AN: 3478

EpiCase AF: 0.0248

EpiControl AF: 0.0270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.057
DANN	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2072392; hg19: chr22-18226612;