Genetic Variant BIRC6:p.Gly4Gly (chr2-32357173-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_016252.4(BIRC6):c.12T>C(p.Gly4Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 1,525,628 control chromosomes in the GnomAD database, including 399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. G4G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.032 ( 164 hom., cov: 32)

Exomes 𝑓: 0.013 ( 235 hom. )

Consequence

BIRC6
NM_016252.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0640

Publications

3 publications found

Variant links:

Genes affected

BIRC6 (HGNC:13516): (baculoviral IAP repeat containing 6) This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination. [provided by RefSeq, Jul 2008]

BIRC6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-32357173-T-C is Benign according to our data. Variant chr2-32357173-T-C is described in ClinVar as Benign. ClinVar VariationId is 3037379.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.064 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016252.4. 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
	BIRC6	NM_016252.4	MANE Select	c.12T>C	p.Gly4Gly	synonymous	Exon 1 of 74	NP_057336.3	Q9NR09
	BIRC6	NM_001378125.1		c.-73T>C		upstream_gene	N/A	NP_001365054.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BIRC6	ENST00000421745.7	TSL:1 MANE Select	c.12T>C	p.Gly4Gly	synonymous	Exon 1 of 74	ENSP00000393596.2	Q9NR09
BIRC6	ENST00000700518.1		c.12T>C	p.Gly4Gly	synonymous	Exon 1 of 73	ENSP00000515025.1	A0A8V8TQB4
BIRC6	ENST00000700519.1		c.12T>C	p.Gly4Gly	synonymous	Exon 1 of 74	ENSP00000515026.1	A0A8V8TR92

Frequencies

GnomAD3 genomes

AF:

0.0316

AC:

4814

AN:

152126

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0868

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.00950

AC:

1318

AN:

138700

AF XY:

0.00917

show subpopulations

Gnomad AFR exome

AF:

0.0757

Gnomad AMR exome

AF:

0.00680

Gnomad ASJ exome

AF:

0.00649

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00594

GnomAD4 exome

AF:

0.0130

AC:

17902

AN:

1373394

Hom.:

235

Cov.:

AF XY:

0.0127

AC XY:

8629

AN XY:

680438

show subpopulations

African (AFR)

AF:

0.0896

AC:

2501

AN:

27906

American (AMR)

AF:

0.00848

AC:

268

AN:

31594

Ashkenazi Jewish (ASJ)

AF:

0.00707

AC:

169

AN:

23916

East Asian (EAS)

AF:

0.0000311

AC:

AN:

32176

South Asian (SAS)

AF:

0.00443

AC:

340

AN:

76680

European-Finnish (FIN)

AF:

0.00292

AC:

119

AN:

40800

Middle Eastern (MID)

AF:

0.0133

AC:

AN:

5476

European-Non Finnish (NFE)

AF:

0.0126

AC:

13590

AN:

1077942

Other (OTH)

AF:

0.0148

AC:

841

AN:

56904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

881

1761

2642

3522

4403

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.0317

AC:

4828

AN:

152234

Hom.:

164

Cov.:

AF XY:

0.0312

AC XY:

2322

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0869

AC:

3611

AN:

41556

American (AMR)

AF:

0.0155

AC:

237

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.000387

AC:

AN:

5162

South Asian (SAS)

AF:

0.00352

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00236

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0124

AC:

841

AN:

67992

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

246

493

739

986

1232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0175

Hom.:

Bravo

AF:

0.0353

Asia WGS

AF:

0.00694

AC:

AN:

3472

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

BIRC6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.064

PromoterAI

0.0046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over