Variant 17-78223510-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.141

Variant links:

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]

BIRC5 links:

BIRC5 (HGNC:):

BIRC5 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
BIRC5	NM_001168.3 linkuse as main transcript	c.385G>A	p.Glu129Lys	missense_variant	4/4	ENST00000350051.8	NP_001159.2	O15392A0A0B4J1S3
BIRC5	NM_001012271.2 linkuse as main transcript	c.454G>A	p.Glu152Lys	missense_variant	5/5		NP_001012271.1	O15392H3BLT4
BIRC5	NM_001012270.2 linkuse as main transcript	c.267G>A	p.Arg89Arg	synonymous_variant	3/3		NP_001012270.1	O15392-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8 linkuse as main transcript	c.385G>A	p.Glu129Lys	missense_variant	4/4	1	NM_001168.3	ENSP00000324180.4		A0A0B4J1S3

Frequencies

GnomAD3 genomes

AF:

0.953

AC:

145127

AN:

152220

Hom.:

69282

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.940

AC XY:

681727

AN XY:

724946

show subpopulations

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.:

AF XY:

0.951

AC XY:

70837

AN XY:

74480

show subpopulations

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

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

LIST_S2

Benign

0.11

T;T

MetaRNN

Benign

7.1e-7

T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.33

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over