chr22-17743846-A-G

Variant names:

• chr22-17743846-A-G
• rs2072392
• NM_001196.4:c.180T>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.180T>C​(p.Asp60Asp) 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
• Publications: 15 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=-0.83).
• 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BID	NM_001196.4	MANE Select	c.180T>C	p.Asp60Asp	synonymous	Exon 3 of 6	NP_001187.1
	BID	NM_197966.3		c.318T>C	p.Asp106Asp	synonymous	Exon 3 of 6	NP_932070.1
	BID	NM_001244567.1		c.180T>C	p.Asp60Asp	synonymous	Exon 3 of 6	NP_001231496.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BID	ENST00000622694.5	TSL:1 MANE Select	c.180T>C	p.Asp60Asp	synonymous	Exon 3 of 6	ENSP00000480414.1
	BID	ENST00000317361.11	TSL:1	c.318T>C	p.Asp106Asp	synonymous	Exon 3 of 6	ENSP00000318822.7
	BID	ENST00000551952.5	TSL:1	c.180T>C	p.Asp60Asp	synonymous	Exon 3 of 6	ENSP00000449236.1

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

GnomAD2 exomes AF: 0.0278 AC: 6908 AN: 248342 AF XY: 0.0265

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 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

African (AFR) AF: 0.0827 AC: 2768 AN: 33464

American (AMR) AF: 0.0185 AC: 828 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 798 AN: 26128

East Asian (EAS) AF: 0.0975 AC: 3871 AN: 39694

South Asian (SAS) AF: 0.00906 AC: 781 AN: 86248

European-Finnish (FIN) AF: 0.00510 AC: 267 AN: 52306

Middle Eastern (MID) AF: 0.0297 AC: 169 AN: 5698

European-Non Finnish (NFE) AF: 0.0239 AC: 26566 AN: 1111758

Other (OTH) AF: 0.0299 AC: 1804 AN: 60332

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

African (AFR) AF: 0.0822 AC: 3418 AN: 41560

American (AMR) AF: 0.0258 AC: 395 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0265 AC: 92 AN: 3472

East Asian (EAS) AF: 0.0868 AC: 450 AN: 5182

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4830

European-Finnish (FIN) AF: 0.00301 AC: 32 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0235 AC: 1597 AN: 68016

Other (OTH) AF: 0.0399 AC: 84 AN: 2106

Alfa AF: 0.0307 Hom.: 98

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.057
DANN	Benign	0.33
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=300/0	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: rs2072392; hg19: chr22-18226612;