17-78214076-C-T

Variant names:

• chr17-78214076-C-T
• rs17878467
• NM_001168.3:c.-241C>T

Variant summary

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

The NM_001168.3(BIRC5):​c.-241C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 513,782 control chromosomes in the GnomAD database, including 2,636 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 0.076 (638 hom., cov: 32)
  • Exomes 𝑓: 0.093 (1998 hom.)
• Consequence: BIRC5 NM_001168.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 24 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168.3. 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.-241C>T		upstream_gene	N/A	NP_001159.2
	BIRC5	NM_001012271.2		c.-241C>T		upstream_gene	N/A	NP_001012271.1
	BIRC5	NM_001012270.2		c.-241C>T		upstream_gene	N/A	NP_001012270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC5	ENST00000350051.8	TSL:1 MANE Select	c.-241C>T		upstream_gene	N/A	ENSP00000324180.4
	BIRC5	ENST00000301633.8	TSL:1	c.-241C>T		upstream_gene	N/A	ENSP00000301633.3
	BIRC5	ENST00000374948.6	TSL:1	c.-241C>T		upstream_gene	N/A	ENSP00000364086.1

Frequencies

GnomAD3 genomes AF: 0.0763 AC: 11602 AN: 152090 Hom.: 640 Cov.: 32

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0497

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0928 AC: 33570 AN: 361574 Hom.: 1998 AF XY: 0.0931 AC XY: 17693 AN XY: 190094

African (AFR) AF: 0.0252 AC: 182 AN: 7230

American (AMR) AF: 0.0787 AC: 783 AN: 9950

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 1508 AN: 11300

East Asian (EAS) AF: 0.000225 AC: 5 AN: 22234

South Asian (SAS) AF: 0.0764 AC: 2864 AN: 37496

European-Finnish (FIN) AF: 0.0442 AC: 1191 AN: 26954

Middle Eastern (MID) AF: 0.146 AC: 236 AN: 1620

European-Non Finnish (NFE) AF: 0.111 AC: 24731 AN: 223160

Other (OTH) AF: 0.0957 AC: 2070 AN: 21630

GnomAD4 genome AF: 0.0762 AC: 11595 AN: 152208 Hom.: 638 Cov.: 32 AF XY: 0.0733 AC XY: 5456 AN XY: 74432

African (AFR) AF: 0.0205 AC: 850 AN: 41532

American (AMR) AF: 0.0966 AC: 1477 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5170

South Asian (SAS) AF: 0.0808 AC: 390 AN: 4826

European-Finnish (FIN) AF: 0.0394 AC: 418 AN: 10610

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7661 AN: 67990

Other (OTH) AF: 0.105 AC: 223 AN: 2114

Alfa AF: 0.0811 Hom.: 77

Bravo AF: 0.0767

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	10
DANN	Benign	0.94
PhyloP100		1.6
PromoterAI		-0.034	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17878467; hg19: chr17-76210157;