rs17879146

Variant names:

• chr17-78223864-T-G
• rs17879146
• NM_001168.3:c.*310T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001168.3(BIRC5):​c.*310T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 492,660 control chromosomes in the GnomAD database, including 79 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 0.012 (19 hom., cov: 32)
  • Exomes 𝑓: 0.016 (60 hom.)
• Consequence: BIRC5 NM_001168.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 6 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]

ENSG00000308650 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0116 (1767/152320) while in subpopulation SAS AF = 0.0249 (120/4828). AF 95% confidence interval is 0.0212. There are 19 homozygotes in GnomAd4. There are 802 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1767 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC5	NM_001168.3	MANE Select	c.*310T>G		3_prime_UTR	Exon 4 of 4	NP_001159.2	A0A0B4J1S3
	BIRC5	NM_001012271.2		c.*310T>G		3_prime_UTR	Exon 5 of 5	NP_001012271.1	H3BLT4
	BIRC5	NM_001012270.2		c.*207T>G		3_prime_UTR	Exon 3 of 3	NP_001012270.1	O15392-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC5	ENST00000350051.8	TSL:1 MANE Select	c.*310T>G		3_prime_UTR	Exon 4 of 4	ENSP00000324180.4	A0A0B4J1S3
	BIRC5	ENST00000301633.8	TSL:1	c.*310T>G		3_prime_UTR	Exon 5 of 5	ENSP00000301633.3	H3BLT4
	BIRC5	ENST00000374948.6	TSL:1	c.*207T>G		3_prime_UTR	Exon 3 of 3	ENSP00000364086.1	O15392-3

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1769 AN: 152202 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00355

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0250

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.0122 AC: 302 AN: 24662 AF XY: 0.0125

Gnomad AFR exome AF: 0.00235

Gnomad AMR exome AF: 0.00453

Gnomad ASJ exome AF: 0.0313

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00750

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.00775

GnomAD4 exome AF: 0.0157 AC: 5335 AN: 340340 Hom.: 60 Cov.: 5 AF XY: 0.0166 AC XY: 2918 AN XY: 175604

African (AFR) AF: 0.00250 AC: 23 AN: 9202

American (AMR) AF: 0.00653 AC: 64 AN: 9808

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 394 AN: 11004

East Asian (EAS) AF: 0.00 AC: 0 AN: 23478

South Asian (SAS) AF: 0.0226 AC: 568 AN: 25126

European-Finnish (FIN) AF: 0.00467 AC: 106 AN: 22686

Middle Eastern (MID) AF: 0.00562 AC: 9 AN: 1600

European-Non Finnish (NFE) AF: 0.0177 AC: 3841 AN: 216960

Other (OTH) AF: 0.0161 AC: 330 AN: 20476

GnomAD4 genome AF: 0.0116 AC: 1767 AN: 152320 Hom.: 19 Cov.: 32 AF XY: 0.0108 AC XY: 802 AN XY: 74486

African (AFR) AF: 0.00353 AC: 147 AN: 41588

American (AMR) AF: 0.00948 AC: 145 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4828

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0171 AC: 1161 AN: 68004

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.0140 Hom.: 6

Bravo AF: 0.0115

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.85
DANN	Benign	0.65
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17879146; hg19: chr17-76219945;