rs8190315

Variant names:

• chr22-17743998-T-C
• rs8190315
• NM_001196.4:c.28A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict 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 (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
• Publications: 34 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 -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.

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.28A>G	p.Ser10Gly	missense	Exon 3 of 6	NP_001187.1	A8ASI8
	BID	NM_197966.3		c.166A>G	p.Ser56Gly	missense	Exon 3 of 6	NP_932070.1	P55957-2
	BID	NM_001244567.1		c.28A>G	p.Ser10Gly	missense	Exon 3 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.28A>G	p.Ser10Gly	missense	Exon 3 of 6	ENSP00000480414.1	P55957-1
	BID	ENST00000317361.11	TSL:1	c.166A>G	p.Ser56Gly	missense	Exon 3 of 6	ENSP00000318822.7	P55957-2
	BID	ENST00000551952.5	TSL:1	c.28A>G	p.Ser10Gly	missense	Exon 3 of 6	ENSP00000449236.1	P55957-1

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

GnomAD2 exomes AF: 0.0238 AC: 5968 AN: 251168 AF XY: 0.0224

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 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

African (AFR) AF: 0.0786 AC: 2630 AN: 33478

American (AMR) AF: 0.0145 AC: 648 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 548 AN: 26130

East Asian (EAS) AF: 0.0972 AC: 3857 AN: 39696

South Asian (SAS) AF: 0.00858 AC: 740 AN: 86228

European-Finnish (FIN) AF: 0.00327 AC: 174 AN: 53258

Middle Eastern (MID) AF: 0.0239 AC: 138 AN: 5768

European-Non Finnish (NFE) AF: 0.0186 AC: 20697 AN: 1111872

Other (OTH) AF: 0.0256 AC: 1546 AN: 60386

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

African (AFR) AF: 0.0784 AC: 3254 AN: 41528

American (AMR) AF: 0.0233 AC: 357 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.0860 AC: 445 AN: 5176

South Asian (SAS) AF: 0.00788 AC: 38 AN: 4822

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0182 AC: 1241 AN: 68010

Other (OTH) AF: 0.0383 AC: 81 AN: 2114

Alfa AF: 0.0259 Hom.: 318

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 v4.9

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
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00029	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-0.69
PrimateAI	Benign	0.25	T
PROVEAN	Benign	1.7	N
REVEL	Benign	0.014
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	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
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

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