dbSNP rs17879146: BIRC5:c.*310T>G (chr17-78223864-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.264

Publications

6 publications found

Variant links:

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]

BIRC5 links:

ENSG00000308650 (HGNC:):

ENSG00000308650 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BIRC5	NM_001168.3 link	c.*310T>G	3_prime_UTR_variant	Exon 4 of 4	ENST00000350051.8	NP_001159.2	O15392A0A0B4J1S3
BIRC5	NM_001012271.2 link	c.*310T>G	3_prime_UTR_variant	Exon 5 of 5		NP_001012271.1	O15392H3BLT4
BIRC5	NM_001012270.2 link	c.*207T>G	3_prime_UTR_variant	Exon 3 of 3		NP_001012270.1	O15392-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC5	ENST00000350051.8 link	c.*310T>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001168.3	ENSP00000324180.4		A0A0B4J1S3

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1769

AN:

152202

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.0166

AC XY:

2918

AN XY:

175604

show subpopulations

African (AFR)

AF:

0.00250

AC:

AN:

9202

American (AMR)

AF:

0.00653

AC:

AN:

9808

Ashkenazi Jewish (ASJ)

AF:

0.0358

AC:

394

AN:

11004

East Asian (EAS)

AF:

0.00

AC:

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:

AN:

1600

European-Non Finnish (NFE)

AF:

0.0177

AC:

3841

AN:

216960

Other (OTH)

AF:

0.0161

AC:

330

AN:

20476

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

247

494

741

988

1235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0116

AC:

1767

AN:

152320

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

802

AN XY:

74486

show subpopulations

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:

AN:

5192

South Asian (SAS)

AF:

0.0249

AC:

120

AN:

4828

European-Finnish (FIN)

AF:

0.00226

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0171

AC:

1161

AN:

68004

Other (OTH)

AF:

0.0142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

175

263

350

438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0140

Hom.:

Bravo

AF:

0.0115

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.85

(source)

DANN

Benign

0.65

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over