rs190798003

Variant names:

• chr11-102350026-G-A
• rs190798003
• NM_001166.5:c.172G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-102350026-G-A
• chr11-102350026-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001166.5(BIRC2):​c.172G>A​(p.Ala58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A58S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: BIRC2 NM_001166.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.58

Genes affected

BIRC2 (HGNC:590): (baculoviral IAP repeat containing 2) The protein encoded by this gene is a member of a family of proteins that inhibits apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. This encoded protein inhibits apoptosis induced by serum deprivation and menadione, a potent inducer of free radicals. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057353616).
• BS2: High AC in GnomAdExome4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC2	NM_001166.5	c.172G>A	p.Ala58Thr	missense_variant	Exon 2 of 9	ENST00000227758.7	NP_001157.1
BIRC2	NM_001256163.1	c.172G>A	p.Ala58Thr	missense_variant	Exon 2 of 9		NP_001243092.1
BIRC2	NM_001256166.2	c.25G>A	p.Ala9Thr	missense_variant	Exon 2 of 9		NP_001243095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC2	ENST00000227758.7	c.172G>A	p.Ala58Thr	missense_variant	Exon 2 of 9	1	NM_001166.5	ENSP00000227758.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000137 AC: 20 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0030
DANN	Benign	0.72
DEOGEN2	Benign	0.061	.;T;T;T;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.56	T;.;T;T;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.057	T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.52	.;N;.;.;.;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.44	N;N;N;N;.;.
REVEL	Benign	0.022
Sift	Benign	0.32	T;T;T;T;.;.
Sift4G	Benign	0.44	T;T;T;T;T;T
Polyphen		0.0010	.;B;.;.;.;B
Vest4		0.058
MVP		0.49
MPC		0.050
ClinPred		0.13	T
GERP RS		-7.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.072
gMVP		0.16

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: rs190798003; hg19: chr11-102220757;