Genetic Variant NM_001165.5:c.*557G>C (chr11-102337659-G-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_001165.5(BIRC3):c.*557G>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 0.107 in 318,664 control chromosomes in the GnomAD database, including 2,385 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 0.085 ( 725 hom., cov: 32)

Exomes 𝑓: 0.13 ( 1660 hom. )

Consequence

BIRC3
NM_001165.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.170

Publications

12 publications found

Variant links:

Genes affected

BIRC3 (HGNC:591): (baculoviral IAP repeat containing 3) This gene encodes a member of the IAP family of proteins that inhibit apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. The encoded protein inhibits apoptosis induced by serum deprivation but does not affect apoptosis resulting from exposure to menadione, a potent inducer of free radicals. It contains 3 baculovirus IAP repeats and a ring finger domain. Transcript variants encoding the same isoform have been identified. [provided by RefSeq, Aug 2011]

BIRC3 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC3	NM_001165.5 link	c.*557G>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000263464.9	NP_001156.1
BIRC3	NM_182962.3 link	c.*557G>C		3_prime_UTR_variant	Exon 10 of 10		NP_892007.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
BIRC3	ENST00000263464.9 link	c.*557G>C	3_prime_UTR_variant	Exon 9 of 9	1	NM_001165.5	ENSP00000263464.4
BIRC3	ENST00000526421.6 link	c.*557G>C	3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000501119.1
BIRC3	ENST00000532808.5 link	c.*557G>C	3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000432907.1

Frequencies

GnomAD3 genomes

AF:

0.0849

AC:

12917

AN:

152102

Hom.:

728

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0210

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0734

Gnomad ASJ

AF:

0.0606

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.0771

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.0731

GnomAD4 exome

AF:

0.128

AC:

21223

AN:

166444

Hom.:

1660

Cov.:

AF XY:

0.127

AC XY:

10394

AN XY:

81584

show subpopulations

African (AFR)

AF:

0.0232

AC:

137

AN:

5906

American (AMR)

AF:

0.0803

AC:

383

AN:

4772

Ashkenazi Jewish (ASJ)

AF:

0.0665

AC:

501

AN:

7538

East Asian (EAS)

AF:

0.281

AC:

4934

AN:

17562

South Asian (SAS)

AF:

0.0768

AC:

110

AN:

1432

European-Finnish (FIN)

AF:

0.119

AC:

1003

AN:

8404

Middle Eastern (MID)

AF:

0.0981

AC:

AN:

968

European-Non Finnish (NFE)

AF:

0.119

AC:

12827

AN:

107862

Other (OTH)

AF:

0.103

AC:

1233

AN:

12000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

910

1820

2729

3639

4549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.0848

AC:

12907

AN:

152220

Hom.:

725

Cov.:

AF XY:

0.0855

AC XY:

6366

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0210

AC:

871

AN:

41566

American (AMR)

AF:

0.0731

AC:

1118

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0606

AC:

210

AN:

3468

East Asian (EAS)

AF:

0.208

AC:

1078

AN:

5182

South Asian (SAS)

AF:

0.0774

AC:

373

AN:

4818

European-Finnish (FIN)

AF:

0.106

AC:

1116

AN:

10572

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7925

AN:

68004

Other (OTH)

AF:

0.0709

AC:

150

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

612

1224

1835

2447

3059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0993

Hom.:

122

Bravo

AF:

0.0808

Asia WGS

AF:

0.102

AC:

354

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.1

(source)

DANN

Benign

0.74

PhyloP100

-0.17

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