rs11538

Variant names:

• chr22-17738065-A-G
• rs11538
• NM_001196.4:c.528T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001196.4(BID):​c.528T>C​(p.Asn176Asn) 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
• Publications: 26 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001196.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BID	NM_001196.4	MANE Select	c.528T>C	p.Asn176Asn	synonymous	Exon 5 of 6	NP_001187.1	A8ASI8
	BID	NM_197966.3		c.666T>C	p.Asn222Asn	synonymous	Exon 5 of 6	NP_932070.1	P55957-2
	BID	NM_001244567.1		c.528T>C	p.Asn176Asn	synonymous	Exon 5 of 6	NP_001231496.1	A8ASI8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BID	ENST00000622694.5	TSL:1 MANE Select	c.528T>C	p.Asn176Asn	synonymous	Exon 5 of 6	ENSP00000480414.1	P55957-1
	BID	ENST00000317361.11	TSL:1	c.666T>C	p.Asn222Asn	synonymous	Exon 5 of 6	ENSP00000318822.7	P55957-2
	BID	ENST00000551952.5	TSL:1	c.528T>C	p.Asn176Asn	synonymous	Exon 5 of 6	ENSP00000449236.1	P55957-1

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

GnomAD2 exomes AF: 0.128 AC: 32218 AN: 251474 AF XY: 0.127

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 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

African (AFR) AF: 0.0446 AC: 1493 AN: 33478

American (AMR) AF: 0.123 AC: 5510 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0996 AC: 2603 AN: 26136

East Asian (EAS) AF: 0.00542 AC: 215 AN: 39700

South Asian (SAS) AF: 0.0592 AC: 5106 AN: 86258

European-Finnish (FIN) AF: 0.190 AC: 10168 AN: 53408

Middle Eastern (MID) AF: 0.0665 AC: 383 AN: 5760

European-Non Finnish (NFE) AF: 0.173 AC: 192022 AN: 1111990

Other (OTH) AF: 0.140 AC: 8483 AN: 60394

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

African (AFR) AF: 0.0500 AC: 2079 AN: 41554

American (AMR) AF: 0.109 AC: 1667 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0939 AC: 326 AN: 3472

East Asian (EAS) AF: 0.00811 AC: 42 AN: 5176

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4830

European-Finnish (FIN) AF: 0.189 AC: 2007 AN: 10594

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11992 AN: 67998

Other (OTH) AF: 0.112 AC: 236 AN: 2116

Alfa AF: 0.148 Hom.: 6217

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.32
PhyloP100		0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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