chr17-78214998-T-G

Variant names:

• chr17-78214998-T-G
• rs4789551
• ENST00000590449.1:c.*205T>G

Variant summary

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

The ENST00000590449.1(BIRC5):​c.*205T>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 0.0000027 in 369,732 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: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: BIRC5 ENST00000590449.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• 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=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.221+209T>G		intron_variant	Intron 2 of 3	ENST00000350051.8	NP_001159.2
BIRC5	NM_001012271.2	c.221+209T>G		intron_variant	Intron 2 of 4		NP_001012271.1
BIRC5	NM_001012270.2	c.221+209T>G		intron_variant	Intron 2 of 2		NP_001012270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8	c.221+209T>G		intron_variant	Intron 2 of 3	1	NM_001168.3	ENSP00000324180.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000270 AC: 1 AN: 369732 Hom.: 0 Cov.: 4 AF XY: 0.00000513 AC XY: 1 AN XY: 194774

African (AFR) AF: 0.00 AC: 0 AN: 10594

American (AMR) AF: 0.00 AC: 0 AN: 17146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11346

East Asian (EAS) AF: 0.00 AC: 0 AN: 23552

South Asian (SAS) AF: 0.00 AC: 0 AN: 44186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21802

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2100

European-Non Finnish (NFE) AF: 0.00000459 AC: 1 AN: 217902

Other (OTH) AF: 0.00 AC: 0 AN: 21104

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.8
DANN	Benign	0.62
PhyloP100		2.1

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

Other links and lift over

dbSNP: rs4789551; hg19: chr17-76211079;