rs8190315

Positions:

• chr22-17743998-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.28A>G​(p.Ser10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,613,790 control chromosomes in the GnomAD database, including 687 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.036 (156 hom., cov: 32)
  • Exomes 𝑓: 0.021 (531 hom.)
• Consequence: BID NM_001196.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685

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]

BID (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019285083).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BID	NM_001196.4	c.28A>G	p.Ser10Gly	missense_variant	3/6	ENST00000622694.5	NP_001187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BID	ENST00000622694.5	c.28A>G	p.Ser10Gly	missense_variant	3/6	1	NM_001196.4	ENSP00000480414.1

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5491 AN: 152140 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0234

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.00808

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0382

GnomAD3 exomes AF: 0.0238 AC: 5968 AN: 251168 Hom.: 122 AF XY: 0.0224 AC XY: 3048 AN XY: 135774

Gnomad AFR exome AF: 0.0789

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.0217

Gnomad EAS exome AF: 0.0840

Gnomad SAS exome AF: 0.00892

Gnomad FIN exome AF: 0.00259

Gnomad NFE exome AF: 0.0177

Gnomad OTH exome AF: 0.0233

GnomAD4 exome AF: 0.0212 AC: 30978 AN: 1461532 Hom.: 531 Cov.: 32 AF XY: 0.0208 AC XY: 15130 AN XY: 727096

Gnomad4 AFR exome AF: 0.0786

Gnomad4 AMR exome AF: 0.0145

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.0972

Gnomad4 SAS exome AF: 0.00858

Gnomad4 FIN exome AF: 0.00327

Gnomad4 NFE exome AF: 0.0186

Gnomad4 OTH exome AF: 0.0256

GnomAD4 genome AF: 0.0361 AC: 5499 AN: 152258 Hom.: 156 Cov.: 32 AF XY: 0.0350 AC XY: 2603 AN XY: 74448

Gnomad4 AFR AF: 0.0784

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.0860

Gnomad4 SAS AF: 0.00788

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.0182

Gnomad4 OTH AF: 0.0383

Alfa AF: 0.0244 Hom.: 114

Bravo AF: 0.0405

TwinsUK AF: 0.0159 AC: 59

ALSPAC AF: 0.0241 AC: 93

ESP6500AA AF: 0.0783 AC: 345

ESP6500EA AF: 0.0190 AC: 163

ExAC AF: 0.0256 AC: 3109

Asia WGS AF: 0.0580 AC: 201 AN: 3478

EpiCase AF: 0.0191

EpiControl AF: 0.0205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.33
DANN	Benign	0.17
DEOGEN2	Benign	0.064	.;T;T;.;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00029	N
LIST_S2	Benign	0.12	T;T;.;T;.;T
MetaRNN	Benign	0.0019	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	.;N;N;N;N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.7	N;.;N;N;N;.
REVEL	Benign	0.014
Sift	Benign	1.0	T;.;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;B;.
Vest4		0.039
MPC		0.15
ClinPred		0.0010	T
GERP RS		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.22

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: rs8190315; hg19: chr22-18226764; COSMIC: COSV58007633; COSMIC: COSV58007633;