rs1042542

Positions:

• chr17-78225347-T-C

Variant summary

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

The NM_001168.3(BIRC5):​c.*1793T>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 0.638 in 152,118 control chromosomes in the GnomAD database, including 30,987 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 0.64 (30986 hom., cov: 33)
  • Exomes 𝑓: 0.63 (1 hom.)
• Consequence: BIRC5 NM_001168.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC5	NM_001168.3	c.*1793T>C		3_prime_UTR_variant	4/4	ENST00000350051.8
BIRC5	NM_001012270.2	c.*1690T>C		3_prime_UTR_variant	3/3
BIRC5	NM_001012271.2	c.*1793T>C		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC5	ENST00000350051.8	c.*1793T>C		3_prime_UTR_variant	4/4	1	NM_001168.3	P1
BIRC5	ENST00000301633.8	c.*1793T>C		3_prime_UTR_variant	5/5	1
BIRC5	ENST00000374948.6	c.*1690T>C		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96905 AN: 151992 Hom.: 30961 Cov.: 33

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.625 AC: 5 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.625 AC XY: 5 AN XY: 8

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.638 AC: 96983 AN: 152110 Hom.: 30986 Cov.: 33 AF XY: 0.639 AC XY: 47491 AN XY: 74356

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.605

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.628

Alfa AF: 0.645 Hom.: 52162

Bravo AF: 0.629

Asia WGS AF: 0.639 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.20

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: rs1042542; hg19: chr17-76221428;