17-78216757-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001168.3(BIRC5):c.315C>T(p.Asp105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,613,712 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (2 hom.)
• Consequence: BIRC5 NM_001168.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0920

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 17-78216757-C-T is Benign according to our data. Variant chr17-78216757-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.092 with no splicing effect.
• BS2: High AC in GnomAd at 191 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC5	NM_001168.3	c.315C>T	p.Asp105=	synonymous_variant	3/4	ENST00000350051.8
BIRC5	NM_001012271.2	c.384C>T	p.Asp128=	synonymous_variant	4/5
BIRC5	NM_001012270.2	c.221+1968C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC5	ENST00000350051.8	c.315C>T	p.Asp105=	synonymous_variant	3/4	1	NM_001168.3	P1

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 191 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00216

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00111 AC: 275 AN: 248418 Hom.: 0 AF XY: 0.000973 AC XY: 131 AN XY: 134574

Gnomad AFR exome AF: 0.000248

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.000233

Gnomad NFE exome AF: 0.00218

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00166 AC: 2419 AN: 1461454 Hom.: 2 Cov.: 30 AF XY: 0.00158 AC XY: 1151 AN XY: 727036

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000376

Gnomad4 NFE exome AF: 0.00208

Gnomad4 OTH exome AF: 0.000894

GnomAD4 genome AF: 0.00125 AC: 191 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000954 AC XY: 71 AN XY: 74446

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00216

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00156 Hom.: 0

Bravo AF: 0.00120

EpiCase AF: 0.00142

EpiControl AF: 0.00172

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

Mar 01, 2024

BIRC5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	12
Dann	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs142377770; hg19: chr17-76212838;