ENST00000301633.8:c.-85C>A

Variant names:

• chr17-78214232-C-A
• rs1396498878
• ENST00000301633.8:c.-85C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000301633.8(BIRC5):​c.-85C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000919 in 1,088,046 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
• Consequence: BIRC5 ENST00000301633.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.965
• Publications: 0 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.-85C>A		upstream_gene_variant		ENST00000350051.8	NP_001159.2
BIRC5	NM_001012271.2	c.-85C>A		upstream_gene_variant			NP_001012271.1
BIRC5	NM_001012270.2	c.-85C>A		upstream_gene_variant			NP_001012270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8	c.-85C>A		upstream_gene_variant		1	NM_001168.3	ENSP00000324180.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.19e-7 AC: 1 AN: 1088046 Hom.: 0 Cov.: 14 AF XY: 0.00000184 AC XY: 1 AN XY: 544676

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24316

American (AMR) AF: 0.00 AC: 0 AN: 30492

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20400

East Asian (EAS) AF: 0.00 AC: 0 AN: 32788

South Asian (SAS) AF: 0.00 AC: 0 AN: 67638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4604

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 823202

Other (OTH) AF: 0.00 AC: 0 AN: 47298

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	6.7
DANN	Benign	0.64
PhyloP100		-0.96
PromoterAI		0.070	Neutral

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: rs1396498878; hg19: chr17-76210313;