rs3460

Positions:

• chr11-102337659-G-C

Variant summary

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

The NM_001165.5(BIRC3):​c.*557G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 318,664 control chromosomes in the GnomAD database, including 2,385 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 0.085 (725 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1660 hom.)
• Consequence: BIRC3 NM_001165.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

Genes affected

BIRC3 (HGNC:591): (baculoviral IAP repeat containing 3) This gene encodes a member of the IAP family of proteins that inhibit apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. The encoded protein inhibits apoptosis induced by serum deprivation but does not affect apoptosis resulting from exposure to menadione, a potent inducer of free radicals. It contains 3 baculovirus IAP repeats and a ring finger domain. Transcript variants encoding the same isoform have been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC3	NM_001165.5	c.*557G>C		3_prime_UTR_variant	9/9	ENST00000263464.9	NP_001156.1
BIRC3	NM_182962.3	c.*557G>C		3_prime_UTR_variant	10/10		NP_892007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC3	ENST00000263464.9	c.*557G>C		3_prime_UTR_variant	9/9	1	NM_001165.5	ENSP00000263464	P1
BIRC3	ENST00000526421.6	c.*557G>C		3_prime_UTR_variant	10/10	2		ENSP00000501119	P1
BIRC3	ENST00000532808.5	c.*557G>C		3_prime_UTR_variant	10/10	5		ENSP00000432907	P1

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 12917 AN: 152102 Hom.: 728 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0734

Gnomad ASJ AF: 0.0606

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0731

GnomAD4 exome AF: 0.128 AC: 21223 AN: 166444 Hom.: 1660 Cov.: 0 AF XY: 0.127 AC XY: 10394 AN XY: 81584

Gnomad4 AFR exome AF: 0.0232

Gnomad4 AMR exome AF: 0.0803

Gnomad4 ASJ exome AF: 0.0665

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.0768

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.0848 AC: 12907 AN: 152220 Hom.: 725 Cov.: 32 AF XY: 0.0855 AC XY: 6366 AN XY: 74414

Gnomad4 AFR AF: 0.0210

Gnomad4 AMR AF: 0.0731

Gnomad4 ASJ AF: 0.0606

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.0774

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0709

Alfa AF: 0.0993 Hom.: 122

Bravo AF: 0.0808

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.74

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: rs3460; hg19: chr11-102208390;