rs1042489

Positions:

• chr17-78224125-T-C
• chr17-78224125-T-G

Variant summary

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

The NM_001168.3(BIRC5):​c.*571T>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 0.395 in 150,266 control chromosomes in the GnomAD database, including 11,847 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 0.40 (11830 hom., cov: 27)
  • Exomes 𝑓: 0.18 (17 hom.)
• Consequence: BIRC5 NM_001168.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.*571T>C		3_prime_UTR_variant	4/4	ENST00000350051.8	NP_001159.2
BIRC5	NM_001012271.2	c.*571T>C		3_prime_UTR_variant	5/5		NP_001012271.1
BIRC5	NM_001012270.2	c.*468T>C		3_prime_UTR_variant	3/3		NP_001012270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8	c.*571T>C		3_prime_UTR_variant	4/4	1	NM_001168.3	ENSP00000324180.4
BIRC5	ENST00000301633.8	c.*571T>C		3_prime_UTR_variant	5/5	1		ENSP00000301633.3
BIRC5	ENST00000374948.6	c.*468T>C		3_prime_UTR_variant	3/3	1		ENSP00000364086.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 59163 AN: 149584 Hom.: 11822 Cov.: 27

Gnomad AFR AF: 0.445

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.179 AC: 104 AN: 582 Hom.: 17 Cov.: 0 AF XY: 0.172 AC XY: 51 AN XY: 296

Gnomad4 AFR exome AF: 0.0667

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.396 AC: 59200 AN: 149684 Hom.: 11830 Cov.: 27 AF XY: 0.394 AC XY: 28721 AN XY: 72930

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.393

Alfa AF: 0.372 Hom.: 14028

Bravo AF: 0.405

Asia WGS AF: 0.399 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1042489; hg19: chr17-76220206;