rs4789551

Variant names:

• chr17-78214998-T-C
• rs4789551
• ENST00000590449.1:c.*205T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-78214998-T-C
• chr17-78214998-T-G

Variant summary

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

The ENST00000590449.1(BIRC5):​c.*205T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 521,728 control chromosomes in the GnomAD database, including 2,708 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 0.11 (1118 hom., cov: 33)
  • Exomes 𝑓: 0.085 (1590 hom.)
• Consequence: BIRC5 ENST00000590449.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 10 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590449.1. 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.221+209T>C		intron	N/A	NP_001159.2	A0A0B4J1S3
	BIRC5	NM_001012271.2		c.221+209T>C		intron	N/A	NP_001012271.1	H3BLT4
	BIRC5	NM_001012270.2		c.221+209T>C		intron	N/A	NP_001012270.1	O15392-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC5	ENST00000590449.1	TSL:1	c.*205T>C		3_prime_UTR	Exon 2 of 2	ENSP00000465868.1	O15392-7
	BIRC5	ENST00000350051.8	TSL:1 MANE Select	c.221+209T>C		intron	N/A	ENSP00000324180.4	A0A0B4J1S3
	BIRC5	ENST00000301633.8	TSL:1	c.221+209T>C		intron	N/A	ENSP00000301633.3	H3BLT4

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16481 AN: 152072 Hom.: 1117 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0744

Gnomad OTH AF: 0.0894

GnomAD4 exome AF: 0.0850 AC: 31404 AN: 369538 Hom.: 1590 Cov.: 4 AF XY: 0.0843 AC XY: 16416 AN XY: 194658

African (AFR) AF: 0.186 AC: 1970 AN: 10580

American (AMR) AF: 0.150 AC: 2574 AN: 17134

Ashkenazi Jewish (ASJ) AF: 0.0926 AC: 1050 AN: 11340

East Asian (EAS) AF: 0.112 AC: 2638 AN: 23530

South Asian (SAS) AF: 0.0844 AC: 3727 AN: 44174

European-Finnish (FIN) AF: 0.0417 AC: 909 AN: 21788

Middle Eastern (MID) AF: 0.0414 AC: 87 AN: 2100

European-Non Finnish (NFE) AF: 0.0763 AC: 16617 AN: 217800

Other (OTH) AF: 0.0869 AC: 1832 AN: 21092

GnomAD4 genome AF: 0.108 AC: 16488 AN: 152190 Hom.: 1118 Cov.: 33 AF XY: 0.107 AC XY: 7960 AN XY: 74428

African (AFR) AF: 0.185 AC: 7681 AN: 41516

American (AMR) AF: 0.114 AC: 1745 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3470

East Asian (EAS) AF: 0.104 AC: 540 AN: 5178

South Asian (SAS) AF: 0.0943 AC: 455 AN: 4826

European-Finnish (FIN) AF: 0.0417 AC: 442 AN: 10606

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0744 AC: 5059 AN: 68004

Other (OTH) AF: 0.0880 AC: 186 AN: 2114

Alfa AF: 0.0863 Hom.: 1139

Bravo AF: 0.121

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	9.1
DANN	Benign	0.66
PhyloP100		2.1
Mutation Taster		=98/2	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: rs4789551; hg19: chr17-76211079;