rs2239680

Positions:

• chr17-78223702-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.*148T>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 0.27 in 1,447,208 control chromosomes in the GnomAD database, including 53,845 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 0.24 (4545 hom., cov: 33)
  • Exomes 𝑓: 0.27 (49300 hom.)
• Consequence: BIRC5 NM_001168.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.747

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC5	NM_001168.3	c.*148T>C		3_prime_UTR_variant	4/4	ENST00000350051.8
BIRC5	NM_001012270.2	c.*45T>C		3_prime_UTR_variant	3/3
BIRC5	NM_001012271.2	c.*148T>C		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC5	ENST00000350051.8	c.*148T>C		3_prime_UTR_variant	4/4	1	NM_001168.3	P1
BIRC5	ENST00000301633.8	c.*148T>C		3_prime_UTR_variant	5/5	1
BIRC5	ENST00000374948.6	c.*45T>C		3_prime_UTR_variant	3/3	1
BIRC5	ENST00000589892.1	n.593T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36177 AN: 151860 Hom.: 4541 Cov.: 33

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.270 AC: 26095 AN: 96698 Hom.: 3387 AF XY: 0.274 AC XY: 13890 AN XY: 50748

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.249

Gnomad EAS exome AF: 0.264

Gnomad SAS exome AF: 0.251

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.281

GnomAD4 exome AF: 0.273 AC: 354009 AN: 1295230 Hom.: 49300 Cov.: 26 AF XY: 0.272 AC XY: 171331 AN XY: 629766

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.281

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.238 AC: 36203 AN: 151978 Hom.: 4545 Cov.: 33 AF XY: 0.240 AC XY: 17827 AN XY: 74300

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.231

Alfa AF: 0.258 Hom.: 3750

Bravo AF: 0.224

Asia WGS AF: 0.244 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.64
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: rs2239680; hg19: chr17-76219783; COSMIC: COSV56955892; COSMIC: COSV56955892;