Variant chr17-78222827-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000350051.8(BIRC5):c.340-638G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00723 in 1,536,050 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 50 hom. )

Consequence

BIRC5
ENST00000350051.8 intron

Scores

Splicing: ADA: 0.0003601

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.114

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:

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 (BayesDel_addAF=-0.724997).

BP6

Variant 17-78222827-G-A is Benign according to our data. Variant chr17-78222827-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024828.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 900 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
BIRC5	NM_001168.3 linkuse as main transcript	c.340-638G>A	intron_variant	ENST00000350051.8	NP_001159.2	O15392A0A0B4J1S3
BIRC5	NM_001012271.2 linkuse as main transcript	c.409-638G>A	intron_variant		NP_001012271.1	O15392H3BLT4
BIRC5	NM_001012270.2 linkuse as main transcript	c.222-638G>A	intron_variant		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.340-638G>A		intron_variant		1	NM_001168.3	ENSP00000324180.4		A0A0B4J1S3

Frequencies

GnomAD3 genomes

AF:

0.00591

AC:

900

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00935

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00491

AC:

661

AN:

134524

Hom.:

AF XY:

0.00498

AC XY:

365

AN XY:

73274

show subpopulations

Gnomad AFR exome

AF:

0.00202

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00229

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00302

Gnomad FIN exome

AF:

0.0132

Gnomad NFE exome

AF:

0.00829

Gnomad OTH exome

AF:

0.00483

GnomAD4 exome

AF:

0.00738

AC:

10213

AN:

1383770

Hom.:

Cov.:

AF XY:

0.00727

AC XY:

4964

AN XY:

682832

show subpopulations

Gnomad4 AFR exome

AF:

0.000981

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00175

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00298

Gnomad4 FIN exome

AF:

0.0134

Gnomad4 NFE exome

AF:

0.00837

Gnomad4 OTH exome

AF:

0.00601

GnomAD4 genome

AF:

0.00591

AC:

900

AN:

152280

Hom.:

Cov.:

AF XY:

0.00559

AC XY:

416

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.00935

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00884

Hom.:

Bravo

AF:

0.00474

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00701

AC:

ExAC

AF:

0.00284

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

BIRC5: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.5

DANN

Benign

0.61

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.073

MutationTaster

Benign

1.0

N;N;N;N;N

GERP RS

1.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00036

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.18

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