11-102337659-G-C

Variant names:

• chr11-102337659-G-C
• rs3460
• NM_001165.5:c.*557G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165.5. 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
	BIRC3	NM_001165.5	MANE Select	c.*557G>C		3_prime_UTR	Exon 9 of 9	NP_001156.1
	BIRC3	NM_182962.3		c.*557G>C		3_prime_UTR	Exon 10 of 10	NP_892007.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC3	ENST00000263464.9	TSL:1 MANE Select	c.*557G>C		3_prime_UTR	Exon 9 of 9	ENSP00000263464.4
	BIRC3	ENST00000526421.6	TSL:2	c.*557G>C		3_prime_UTR	Exon 10 of 10	ENSP00000501119.1
	BIRC3	ENST00000532808.5	TSL:5	c.*557G>C		3_prime_UTR	Exon 10 of 10	ENSP00000432907.1

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

African (AFR) AF: 0.0232 AC: 137 AN: 5906

American (AMR) AF: 0.0803 AC: 383 AN: 4772

Ashkenazi Jewish (ASJ) AF: 0.0665 AC: 501 AN: 7538

East Asian (EAS) AF: 0.281 AC: 4934 AN: 17562

South Asian (SAS) AF: 0.0768 AC: 110 AN: 1432

European-Finnish (FIN) AF: 0.119 AC: 1003 AN: 8404

Middle Eastern (MID) AF: 0.0981 AC: 95 AN: 968

European-Non Finnish (NFE) AF: 0.119 AC: 12827 AN: 107862

Other (OTH) AF: 0.103 AC: 1233 AN: 12000

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

African (AFR) AF: 0.0210 AC: 871 AN: 41566

American (AMR) AF: 0.0731 AC: 1118 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0606 AC: 210 AN: 3468

East Asian (EAS) AF: 0.208 AC: 1078 AN: 5182

South Asian (SAS) AF: 0.0774 AC: 373 AN: 4818

European-Finnish (FIN) AF: 0.106 AC: 1116 AN: 10572

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7925 AN: 68004

Other (OTH) AF: 0.0709 AC: 150 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-0.17
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: rs3460; hg19: chr11-102208390;