rs11538

Positions:

• chr22-17738065-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.528T>C​(p.Asn176=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,614,094 control chromosomes in the GnomAD database, including 20,716 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 0.12 (1523 hom., cov: 33)
  • Exomes 𝑓: 0.15 (19193 hom.)
• Consequence: BID NM_001196.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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=-0.92).
• BP7: Synonymous conserved (PhyloP=0.506 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BID	NM_001196.4	c.528T>C	p.Asn176=	synonymous_variant	5/6	ENST00000622694.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BID	ENST00000622694.5	c.528T>C	p.Asn176=	synonymous_variant	5/6	1	NM_001196.4	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18769 AN: 152128 Hom.: 1523 Cov.: 33

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0939

Gnomad EAS AF: 0.00790

Gnomad SAS AF: 0.0517

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.128 AC: 32218 AN: 251474 Hom.: 2545 AF XY: 0.127 AC XY: 17202 AN XY: 135908

Gnomad AFR exome AF: 0.0476

Gnomad AMR exome AF: 0.126

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.00625

Gnomad SAS exome AF: 0.0569

Gnomad FIN exome AF: 0.189

Gnomad NFE exome AF: 0.170

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.155 AC: 225983 AN: 1461848 Hom.: 19193 Cov.: 33 AF XY: 0.152 AC XY: 110446 AN XY: 727214

Gnomad4 AFR exome AF: 0.0446

Gnomad4 AMR exome AF: 0.123

Gnomad4 ASJ exome AF: 0.0996

Gnomad4 EAS exome AF: 0.00542

Gnomad4 SAS exome AF: 0.0592

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.123 AC: 18774 AN: 152246 Hom.: 1523 Cov.: 33 AF XY: 0.122 AC XY: 9045 AN XY: 74442

Gnomad4 AFR AF: 0.0500

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0939

Gnomad4 EAS AF: 0.00811

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.112

Alfa AF: 0.154 Hom.: 4149

Bravo AF: 0.114

Asia WGS AF: 0.0410 AC: 142 AN: 3478

EpiCase AF: 0.165

EpiControl AF: 0.150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11538; hg19: chr22-18220831; COSMIC: COSV58008402; COSMIC: COSV58008402;