dbSNP rs1042489: BIRC5:c.*571T>C (chr17-78224125-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001168.3(BIRC5):c.*571T>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 0.395 in 150,266 control chromosomes in the GnomAD database, including 11,847 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 0.40 ( 11830 hom., cov: 27)

Exomes 𝑓: 0.18 ( 17 hom. )

Consequence

BIRC5
NM_001168.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.174

Publications

28 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:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
BIRC5	NM_001168.3 link	c.*571T>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000350051.8	NP_001159.2	O15392A0A0B4J1S3
BIRC5	NM_001012271.2 link	c.*571T>C	3_prime_UTR_variant	Exon 5 of 5		NP_001012271.1	O15392H3BLT4
BIRC5	NM_001012270.2 link	c.*468T>C	3_prime_UTR_variant	Exon 3 of 3		NP_001012270.1	O15392-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
BIRC5	ENST00000350051.8 link	c.*571T>C	3_prime_UTR_variant	Exon 4 of 4	1	NM_001168.3	ENSP00000324180.4	A0A0B4J1S3
BIRC5	ENST00000301633.8 link	c.*571T>C	3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000301633.3	H3BLT4
BIRC5	ENST00000374948.6 link	c.*468T>C	3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000364086.1	O15392-3
ENSG00000308650	ENST00000835545.1 link	n.352-3050A>G	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

59163

AN:

149584

Hom.:

11822

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.211

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.414

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.436

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.395

GnomAD4 exome

AF:

0.179

AC:

104

AN:

582

Hom.:

Cov.:

AF XY:

0.172

AC XY:

AN XY:

296

show subpopulations

African (AFR)

AF:

0.0667

AC:

AN:

American (AMR)

AF:

0.200

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.175

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.200

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.173

AC:

AN:

404

Other (OTH)

AF:

0.200

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.396

AC:

59200

AN:

149684

Hom.:

11830

Cov.:

AF XY:

0.394

AC XY:

28721

AN XY:

72930

show subpopulations

African (AFR)

AF:

0.444

AC:

18007

AN:

40516

American (AMR)

AF:

0.411

AC:

6156

AN:

14994

Ashkenazi Jewish (ASJ)

AF:

0.414

AC:

1430

AN:

3452

East Asian (EAS)

AF:

0.390

AC:

1994

AN:

5110

South Asian (SAS)

AF:

0.434

AC:

2056

AN:

4732

European-Finnish (FIN)

AF:

0.332

AC:

3339

AN:

10044

Middle Eastern (MID)

AF:

0.479

AC:

140

AN:

292

European-Non Finnish (NFE)

AF:

0.371

AC:

25070

AN:

67562

Other (OTH)

AF:

0.393

AC:

816

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

1589

3178

4767

6356

7945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

570

1140

1710

2280

2850

<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:

0.376

Hom.:

18088

Bravo

AF:

0.405

Asia WGS

AF:

0.399

AC:

1388

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.8

(source)

DANN

Benign

0.73

PhyloP100

-0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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