rs4789551

Positions:

• chr17-78214998-T-C

Variant summary

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

The ENST00000590449.1(BIRC5):​c.*205T>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 0.0918 in 521,728 control chromosomes in the GnomAD database, including 2,708 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 0.11 (1118 hom., cov: 33)
  • Exomes 𝑓: 0.085 (1590 hom.)
• Consequence: BIRC5 ENST00000590449.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15

Genes affected

BIRC5 (HGNC:593): (baculoviral IAP repeat containing 5) This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors, yet low in adult tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.221+209T>C		intron_variant		ENST00000350051.8	NP_001159.2
BIRC5	NM_001012270.2	c.221+209T>C		intron_variant			NP_001012270.1
BIRC5	NM_001012271.2	c.221+209T>C		intron_variant			NP_001012271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8	c.221+209T>C		intron_variant		1	NM_001168.3	ENSP00000324180	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16481 AN: 152072 Hom.: 1117 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.0894

GnomAD4 exome AF: 0.0850 AC: 31404 AN: 369538 Hom.: 1590 Cov.: 4 AF XY: 0.0843 AC XY: 16416 AN XY: 194658

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.0926

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.0844

Gnomad4 FIN exome AF: 0.0417

Gnomad4 NFE exome AF: 0.0763

Gnomad4 OTH exome AF: 0.0869

GnomAD4 genome AF: 0.108 AC: 16488 AN: 152190 Hom.: 1118 Cov.: 33 AF XY: 0.107 AC XY: 7960 AN XY: 74428

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0943

Gnomad4 FIN AF: 0.0417

Gnomad4 NFE AF: 0.0744

Gnomad4 OTH AF: 0.0880

Alfa AF: 0.0817 Hom.: 766

Bravo AF: 0.121

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.1
DANN	Benign	0.66

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: rs4789551; hg19: chr17-76211079;