17-78223510-G-C

Variant names:

• chr17-78223510-G-C
• rs2071214
• NM_001168.3:c.385G>C

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.385G>C​(p.Glu129Gln) variant causes a missense 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. 15/20 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BIRC5 NM_001168.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 59 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]

ENSG00000308650 (HGNC:):

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 (MetaRNN=0.06307921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC5	NM_001168.3	c.385G>C	p.Glu129Gln	missense_variant	Exon 4 of 4	ENST00000350051.8	NP_001159.2
BIRC5	NM_001012271.2	c.454G>C	p.Glu152Gln	missense_variant	Exon 5 of 5		NP_001012271.1
BIRC5	NM_001012270.2	c.267G>C	p.Arg89Arg	synonymous_variant	Exon 3 of 3		NP_001012270.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8	c.385G>C	p.Glu129Gln	missense_variant	Exon 4 of 4	1	NM_001168.3	ENSP00000324180.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1458190 Hom.: 0 Cov.: 60 AF XY: 0.00 AC XY: 0 AN XY: 724996

African (AFR) AF: 0.00 AC: 0 AN: 33318

American (AMR) AF: 0.00 AC: 0 AN: 44032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 85574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110226

Other (OTH) AF: 0.00 AC: 0 AN: 60252

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.7
DANN	Benign	0.94
DEOGEN2	Benign	0.019	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.11	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	.;.
PhyloP100		-0.14
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.0080
Sift	Benign	0.062	T;T
Sift4G	Benign	0.22	T;T
Vest4		0.058
ClinPred		0.094	T
GERP RS		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.43

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: rs2071214; hg19: chr17-76219591;