rs2239680

Variant names:

• chr17-78223702-T-C
• rs2239680
• NM_001168.3:c.*148T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 39 publications found

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]

ENSG00000308650 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.*148T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000350051.8	NP_001159.2
BIRC5	NM_001012271.2	c.*148T>C		3_prime_UTR_variant	Exon 5 of 5		NP_001012271.1
BIRC5	NM_001012270.2	c.*45T>C		3_prime_UTR_variant	Exon 3 of 3		NP_001012270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8	c.*148T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001168.3	ENSP00000324180.4

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

GnomAD2 exomes AF: 0.270 AC: 26095 AN: 96698 AF XY: 0.274

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 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

African (AFR) AF: 0.166 AC: 4651 AN: 28058

American (AMR) AF: 0.163 AC: 3485 AN: 21414

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 4714 AN: 20930

East Asian (EAS) AF: 0.255 AC: 8416 AN: 32946

South Asian (SAS) AF: 0.228 AC: 14278 AN: 62524

European-Finnish (FIN) AF: 0.281 AC: 13192 AN: 46986

Middle Eastern (MID) AF: 0.276 AC: 1224 AN: 4430

European-Non Finnish (NFE) AF: 0.283 AC: 290225 AN: 1024536

Other (OTH) AF: 0.259 AC: 13824 AN: 53406

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

African (AFR) AF: 0.168 AC: 6977 AN: 41500

American (AMR) AF: 0.189 AC: 2889 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3466

East Asian (EAS) AF: 0.257 AC: 1331 AN: 5186

South Asian (SAS) AF: 0.228 AC: 1095 AN: 4808

European-Finnish (FIN) AF: 0.292 AC: 3090 AN: 10580

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19025 AN: 67872

Other (OTH) AF: 0.231 AC: 486 AN: 2106

Alfa AF: 0.250 Hom.: 4737

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
PhyloP100		-0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2239680; hg19: chr17-76219783; COSMIC: COSV56955892; COSMIC: COSV56955892;