rs2071214

chr17-78223510-G-Achr17-78223510-G-Cchr17-78223510-G-T

Variant summary

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

The NM_001168.3(BIRC5):c.385G>A(p.Glu129Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,610,428 control chromosomes in the GnomAD database, including 713,948 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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: 𝑓 0.95 (69344 hom., cov: 33)
  • Exomes 𝑓: 0.94 (644604 hom.)
• Consequence: BIRC5 NM_001168.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

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 (MetaRNN=7.106069E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC5	NM_001168.3	c.385G>A	p.Glu129Lys	missense_variant	4/4	ENST00000350051.8
BIRC5	NM_001012271.2	c.454G>A	p.Glu152Lys	missense_variant	5/5
BIRC5	NM_001012270.2	c.267G>A	p.Arg89=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC5	ENST00000350051.8	c.385G>A	p.Glu129Lys	missense_variant	4/4	1	NM_001168.3	P1

Frequencies

GnomAD3 genomes AF: 0.953 AC: 145127 AN: 152220 Hom.: 69282 Cov.: 33

Gnomad AFR AF: 0.988

Gnomad AMI AF: 0.993

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.949

Gnomad OTH AF: 0.949

GnomAD3 exomes AF: 0.934 AC: 232374 AN: 248764 Hom.: 108796 AF XY: 0.936 AC XY: 125877 AN XY: 134546

Gnomad AFR exome AF: 0.991

Gnomad AMR exome AF: 0.917

Gnomad ASJ exome AF: 0.952

Gnomad EAS exome AF: 0.788

Gnomad SAS exome AF: 0.952

Gnomad FIN exome AF: 0.934

Gnomad NFE exome AF: 0.948

Gnomad OTH exome AF: 0.948

GnomAD4 exome AF: 0.940 AC: 1370317 AN: 1458090 Hom.: 644604 Cov.: 60 AF XY: 0.940 AC XY: 681727 AN XY: 724946

Gnomad4 AFR exome AF: 0.991

Gnomad4 AMR exome AF: 0.918

Gnomad4 ASJ exome AF: 0.955

Gnomad4 EAS exome AF: 0.777

Gnomad4 SAS exome AF: 0.952

Gnomad4 FIN exome AF: 0.934

Gnomad4 NFE exome AF: 0.944

Gnomad4 OTH exome AF: 0.942

GnomAD4 genome AF: 0.953 AC: 145251 AN: 152338 Hom.: 69344 Cov.: 33 AF XY: 0.951 AC XY: 70837 AN XY: 74480

Gnomad4 AFR AF: 0.988

Gnomad4 AMR AF: 0.946

Gnomad4 ASJ AF: 0.958

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.953

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.949

Gnomad4 OTH AF: 0.949

Alfa AF: 0.947 Hom.: 166593

Bravo AF: 0.952

TwinsUK AF: 0.939 AC: 3482

ALSPAC AF: 0.943 AC: 3633

ESP6500AA AF: 0.990 AC: 4364

ESP6500EA AF: 0.953 AC: 8198

ExAC AF: 0.936 AC: 113629

Asia WGS AF: 0.911 AC: 3168 AN: 3478

EpiCase AF: 0.956

EpiControl AF: 0.955

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.76
Dann	Benign	0.78
DEOGEN2	Benign	0.0095	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0061	N
LIST_S2	Benign	0.11	T;T
MetaRNN	Benign	7.1e-7	T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.67	N;N
REVEL	Benign	0.013
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.036
MPC		0.36
ClinPred		0.00063	T
GERP RS		0.41
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

Publications

LitVar

Other links and lift over

dbSNP: rs2071214; hg19: chr17-76219591;