17-78214286-G-C

Variant names:

• chr17-78214286-G-C
• rs9904341
• ENST00000590925.6:n.-31G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000590925.6(BIRC5):​n.-31G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,575,254 control chromosomes in the GnomAD database, including 87,970 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (9262 hom., cov: 34)
  • Exomes 𝑓: 0.33 (78708 hom.)
• Consequence: BIRC5 ENST00000590925.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 91 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590925.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC5	NM_001168.3	MANE Select	c.-31G>C		5_prime_UTR	Exon 1 of 4	NP_001159.2
	BIRC5	NM_001012271.2		c.-31G>C		5_prime_UTR	Exon 1 of 5	NP_001012271.1
	BIRC5	NM_001012270.2		c.-31G>C		5_prime_UTR	Exon 1 of 3	NP_001012270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC5	ENST00000590925.6	TSL:1	n.-31G>C		non_coding_transcript_exon	Exon 1 of 5	ENSP00000467336.1
	BIRC5	ENST00000350051.8	TSL:1 MANE Select	c.-31G>C		5_prime_UTR	Exon 1 of 4	ENSP00000324180.4
	BIRC5	ENST00000301633.8	TSL:1	c.-31G>C		5_prime_UTR	Exon 1 of 5	ENSP00000301633.3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52572 AN: 152124 Hom.: 9249 Cov.: 34

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.362

GnomAD2 exomes AF: 0.375 AC: 78649 AN: 209724 AF XY: 0.368

Gnomad AFR exome AF: 0.353

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.515

Gnomad FIN exome AF: 0.389

Gnomad NFE exome AF: 0.325

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.329 AC: 467739 AN: 1423012 Hom.: 78708 Cov.: 27 AF XY: 0.329 AC XY: 232949 AN XY: 707824

African (AFR) AF: 0.349 AC: 11102 AN: 31848

American (AMR) AF: 0.470 AC: 19371 AN: 41246

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 9078 AN: 25026

East Asian (EAS) AF: 0.517 AC: 19645 AN: 38022

South Asian (SAS) AF: 0.353 AC: 29304 AN: 83122

European-Finnish (FIN) AF: 0.386 AC: 19192 AN: 49728

Middle Eastern (MID) AF: 0.294 AC: 1668 AN: 5670

European-Non Finnish (NFE) AF: 0.311 AC: 338448 AN: 1089528

Other (OTH) AF: 0.339 AC: 19931 AN: 58822

GnomAD4 genome AF: 0.346 AC: 52620 AN: 152242 Hom.: 9262 Cov.: 34 AF XY: 0.349 AC XY: 25949 AN XY: 74442

African (AFR) AF: 0.345 AC: 14324 AN: 41526

American (AMR) AF: 0.397 AC: 6082 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3472

East Asian (EAS) AF: 0.515 AC: 2661 AN: 5172

South Asian (SAS) AF: 0.344 AC: 1662 AN: 4828

European-Finnish (FIN) AF: 0.387 AC: 4110 AN: 10610

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21400 AN: 68010

Other (OTH) AF: 0.364 AC: 771 AN: 2116

Alfa AF: 0.261 Hom.: 978

Bravo AF: 0.351

Asia WGS AF: 0.421 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.49
PhyloP100		-0.34
PromoterAI		0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9904341; hg19: chr17-76210367;