Variant 17-78223604-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000374948.6(BIRC5):c.361G>C(p.Gly121Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,610,766 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0085 ( 10 hom., cov: 33)

Exomes 𝑓: 0.011 ( 104 hom. )

Consequence

BIRC5
ENST00000374948.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0260

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031098425).

BP6

Variant 17-78223604-G-C is Benign according to our data. Variant chr17-78223604-G-C is described in ClinVar as [Benign]. Clinvar id is 2648339.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 1293 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BIRC5	NM_001168.3 linkuse as main transcript	c.*50G>C		3_prime_UTR_variant	4/4	ENST00000350051.8
BIRC5	NM_001012270.2 linkuse as main transcript	c.361G>C	p.Gly121Arg	missense_variant	3/3
BIRC5	NM_001012271.2 linkuse as main transcript	c.*50G>C		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC5	ENST00000350051.8 linkuse as main transcript	c.*50G>C		3_prime_UTR_variant	4/4	1	NM_001168.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00849

AC:

1293

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00845

AC:

2095

AN:

247792

Hom.:

AF XY:

0.00893

AC XY:

1198

AN XY:

134132

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.00711

Gnomad ASJ exome

AF:

0.0174

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00259

Gnomad FIN exome

AF:

0.00385

Gnomad NFE exome

AF:

0.0126

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0108

AC:

15770

AN:

1458422

Hom.:

104

Cov.:

AF XY:

0.0107

AC XY:

7786

AN XY:

725034

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.00787

Gnomad4 ASJ exome

AF:

0.0162

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00249

Gnomad4 FIN exome

AF:

0.00438

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00848

AC:

1292

AN:

152344

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

570

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00192

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00888

TwinsUK

AF:

0.0138

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0119

AC:

102

ExAC

AF:

0.00832

AC:

1010

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

BIRC5: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

Cadd

Benign

3.4

Dann

Benign

0.93

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.84

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

0.81

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.043

Vest4

0.19

MVP

0.39

ClinPred

0.016

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over