rs17878467

Variant names:

• chr17-78214076-C-G
• rs17878467
• NM_001168.3:c.-241C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-78214076-C-G
• chr17-78214076-C-T

Variant summary

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

The NM_001168.3(BIRC5):​c.-241C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BIRC5 NM_001168.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 24 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=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.-241C>G		upstream_gene_variant		ENST00000350051.8	NP_001159.2
BIRC5	NM_001012271.2	c.-241C>G		upstream_gene_variant			NP_001012271.1
BIRC5	NM_001012270.2	c.-241C>G		upstream_gene_variant			NP_001012270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8	c.-241C>G		upstream_gene_variant		1	NM_001168.3	ENSP00000324180.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 361828 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 190232

African (AFR) AF: 0.00 AC: 0 AN: 7230

American (AMR) AF: 0.00 AC: 0 AN: 9952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11314

East Asian (EAS) AF: 0.00 AC: 0 AN: 22234

South Asian (SAS) AF: 0.00 AC: 0 AN: 37502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1624

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 223362

Other (OTH) AF: 0.00 AC: 0 AN: 21646

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 77

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	9.1
DANN	Benign	0.70
PhyloP100		1.6
PromoterAI		0.0033	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17878467; hg19: chr17-76210157;