17-78222827-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The ENST00000587746.5(BIRC5):c.341-1G>A variant causes a splice acceptor 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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 ENST00000587746.5 splice_acceptor
• Scores: Splicing: ADA: 0.0003601
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.114

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 -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 GnomAd at 900 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC5	NM_001168.3	c.340-638G>A		intron_variant		ENST00000350051.8
BIRC5	NM_001012270.2	c.222-638G>A		intron_variant
BIRC5	NM_001012271.2	c.409-638G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC5	ENST00000350051.8	c.340-638G>A		intron_variant		1	NM_001168.3	P1

Frequencies

GnomAD3 genomes AF: 0.00591 AC: 900 AN: 152162 Hom.: 4 Cov.: 33

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.: 3 AF XY: 0.00498 AC XY: 365 AN XY: 73274

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.: 50 Cov.: 32 AF XY: 0.00727 AC XY: 4964 AN XY: 682832

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.: 4 Cov.: 33 AF XY: 0.00559 AC XY: 416 AN XY: 74448

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.: 4

Bravo AF: 0.00474

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.00701 AC: 27

ExAC AF: 0.00284 AC: 45

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
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	N
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

Other links and lift over

dbSNP: rs79069105; hg19: chr17-76218908;