rs1943781

Variant names:

• chr11-102364410-G-A
• rs1943781
• NM_001166.5:c.1123+694G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001166.5(BIRC2):​c.1123+694G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 151,698 control chromosomes in the GnomAD database, including 3,344 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 0.18 (3344 hom., cov: 30)
• Consequence: BIRC2 NM_001166.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166.5. 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
	BIRC2	NM_001166.5	MANE Select	c.1123+694G>A		intron	N/A	NP_001157.1
	BIRC2	NM_001256163.1		c.1123+694G>A		intron	N/A	NP_001243092.1
	BIRC2	NM_001256166.2		c.976+694G>A		intron	N/A	NP_001243095.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC2	ENST00000227758.7	TSL:1 MANE Select	c.1123+694G>A		intron	N/A	ENSP00000227758.2
	BIRC2	ENST00000613397.4	TSL:1	c.1123+694G>A		intron	N/A	ENSP00000477613.1
	BIRC2	ENST00000527910.5	TSL:1	n.2852+694G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26889 AN: 151580 Hom.: 3333 Cov.: 30

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.0980

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00505

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.160

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 26932 AN: 151698 Hom.: 3344 Cov.: 30 AF XY: 0.170 AC XY: 12598 AN XY: 74156

African (AFR) AF: 0.343 AC: 14166 AN: 41264

American (AMR) AF: 0.123 AC: 1874 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.00526 AC: 27 AN: 5136

South Asian (SAS) AF: 0.0415 AC: 200 AN: 4816

European-Finnish (FIN) AF: 0.0591 AC: 624 AN: 10556

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9161 AN: 67920

Other (OTH) AF: 0.158 AC: 332 AN: 2102

Alfa AF: 0.165 Hom.: 3970

Bravo AF: 0.189

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-0.030
Mutation Taster		=100/0	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: rs1943781; hg19: chr11-102235141;