17-78214286-G-C

Position:

• chr17-78214286-G-C

Variant summary

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

The NM_001168.3(BIRC5):​c.-31G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,575,254 control chromosomes in the GnomAD database, including 87,970 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 0.35 (9262 hom., cov: 34)
  • Exomes 𝑓: 0.33 (78708 hom.)
• Consequence: BIRC5 NM_001168.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.-31G>C		5_prime_UTR_variant	1/4	ENST00000350051.8	NP_001159.2
BIRC5	NM_001012271.2	c.-31G>C		5_prime_UTR_variant	1/5		NP_001012271.1
BIRC5	NM_001012270.2	c.-31G>C		5_prime_UTR_variant	1/3		NP_001012270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8	c.-31G>C		5_prime_UTR_variant	1/4	1	NM_001168.3	ENSP00000324180.4

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52572 AN: 152124 Hom.: 9249 Cov.: 34

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.362

GnomAD3 exomes AF: 0.375 AC: 78649 AN: 209724 Hom.: 15128 AF XY: 0.368 AC XY: 42444 AN XY: 115330

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.515

Gnomad SAS exome AF: 0.358

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.329 AC: 467739 AN: 1423012 Hom.: 78708 Cov.: 27 AF XY: 0.329 AC XY: 232949 AN XY: 707824

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.363

Gnomad4 EAS exome AF: 0.517

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.311

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.346 AC: 52620 AN: 152242 Hom.: 9262 Cov.: 34 AF XY: 0.349 AC XY: 25949 AN XY: 74442

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.515

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.364

Alfa AF: 0.261 Hom.: 978

Bravo AF: 0.351

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.49
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: rs9904341; hg19: chr17-76210367;