chr17-78223864-T-G

Position:

• chr17-78223864-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001168.3(BIRC5):​c.*310T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 492,660 control chromosomes in the GnomAD database, including 79 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 0.012 (19 hom., cov: 32)
  • Exomes 𝑓: 0.016 (60 hom.)
• Consequence: BIRC5 NM_001168.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264

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]

BIRC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0116 (1767/152320) while in subpopulation SAS AF= 0.0249 (120/4828). AF 95% confidence interval is 0.0212. There are 19 homozygotes in gnomad4. There are 802 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1767 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.*310T>G		3_prime_UTR_variant	4/4	ENST00000350051.8	NP_001159.2
BIRC5	NM_001012271.2	c.*310T>G		3_prime_UTR_variant	5/5		NP_001012271.1
BIRC5	NM_001012270.2	c.*207T>G		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.*310T>G		3_prime_UTR_variant	4/4	1	NM_001168.3	ENSP00000324180.4
BIRC5	ENST00000301633.8	c.*310T>G		3_prime_UTR_variant	5/5	1		ENSP00000301633.3
BIRC5	ENST00000374948.6	c.*207T>G		3_prime_UTR_variant	3/3	1		ENSP00000364086.1
BIRC5	ENST00000589892.1	n.*8T>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1769 AN: 152202 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00355

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0250

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.0122 AC: 302 AN: 24662 Hom.: 6 AF XY: 0.0125 AC XY: 158 AN XY: 12602

Gnomad AFR exome AF: 0.00235

Gnomad AMR exome AF: 0.00453

Gnomad ASJ exome AF: 0.0313

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0153

Gnomad FIN exome AF: 0.00750

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.00775

GnomAD4 exome AF: 0.0157 AC: 5335 AN: 340340 Hom.: 60 Cov.: 5 AF XY: 0.0166 AC XY: 2918 AN XY: 175604

Gnomad4 AFR exome AF: 0.00250

Gnomad4 AMR exome AF: 0.00653

Gnomad4 ASJ exome AF: 0.0358

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0226

Gnomad4 FIN exome AF: 0.00467

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.0116 AC: 1767 AN: 152320 Hom.: 19 Cov.: 32 AF XY: 0.0108 AC XY: 802 AN XY: 74486

Gnomad4 AFR AF: 0.00353

Gnomad4 AMR AF: 0.00948

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0133 Hom.: 2

Bravo AF: 0.0115

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.85
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17879146; hg19: chr17-76219945;