22-17735444-T-C

Position:

• chr22-17735444-T-C

Variant summary

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

The NM_001196.4(BID):​c.*136A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 920,664 control chromosomes in the GnomAD database, including 875 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 0.036 (108 hom., cov: 33)
  • Exomes 𝑓: 0.039 (767 hom.)
• Consequence: BID NM_001196.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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 = 0.0775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BID	NM_001196.4	c.*136A>G		3_prime_UTR_variant	6/6	ENST00000622694.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BID	ENST00000622694.5	c.*136A>G		3_prime_UTR_variant	6/6	1	NM_001196.4	P1

Frequencies

GnomAD3 genomes AF: 0.0363 AC: 5519 AN: 152202 Hom.: 108 Cov.: 33

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0841

Gnomad EAS AF: 0.0838

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.00462

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0406

GnomAD4 exome AF: 0.0394 AC: 30245 AN: 768344 Hom.: 767 Cov.: 10 AF XY: 0.0393 AC XY: 15710 AN XY: 399516

Gnomad4 AFR exome AF: 0.0381

Gnomad4 AMR exome AF: 0.0242

Gnomad4 ASJ exome AF: 0.0828

Gnomad4 EAS exome AF: 0.0986

Gnomad4 SAS exome AF: 0.0382

Gnomad4 FIN exome AF: 0.00674

Gnomad4 NFE exome AF: 0.0374

Gnomad4 OTH exome AF: 0.0433

GnomAD4 genome AF: 0.0363 AC: 5528 AN: 152320 Hom.: 108 Cov.: 33 AF XY: 0.0350 AC XY: 2606 AN XY: 74488

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.0297

Gnomad4 ASJ AF: 0.0841

Gnomad4 EAS AF: 0.0840

Gnomad4 SAS AF: 0.0358

Gnomad4 FIN AF: 0.00462

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0406

Alfa AF: 0.0360 Hom.: 49

Bravo AF: 0.0386

Asia WGS AF: 0.0620 AC: 216 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	0.060
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2305001; hg19: chr22-18218210; COSMIC: COSV58007335; COSMIC: COSV58007335;