Genetic Variant GSDMB:c.407+65A>G (chr17-39912261-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_001165958.2(GSDMB):c.407+65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,191,348 control chromosomes in the GnomAD database, including 166,169 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 0.57 ( 25488 hom., cov: 31)

Exomes 𝑓: 0.52 ( 140681 hom. )

Consequence

GSDMB
NM_001165958.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.833

Publications

23 publications found

Variant links:

Genes affected

GSDMB (HGNC:23690): (gasdermin B) This gene encodes a member of the gasdermin-domain containing protein family. Other gasdermin-family genes are implicated in the regulation of apoptosis in epithelial cells, and are linked to cancer. Alternative splicing and the use of alternative promoters results in multiple transcript variants. Additional variants have been described, but they are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. [provided by RefSeq, Nov 2016]

GSDMB 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMB	NM_001165958.2 link	c.407+65A>G		intron_variant	Intron 3 of 10	ENST00000418519.6	NP_001159430.1	Q8TAX9-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6 link	c.407+65A>G		intron_variant	Intron 3 of 10	5	NM_001165958.2	ENSP00000415049.1		Q8TAX9-4

Frequencies

GnomAD3 genomes

AF:

0.571

AC:

86769

AN:

151888

Hom.:

25474

Cov.:

show subpopulations

Gnomad AFR

AF:

0.698

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.581

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.729

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.633

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.581

GnomAD4 exome

AF:

0.515

AC:

535620

AN:

1039342

Hom.:

140681

AF XY:

0.517

AC XY:

274014

AN XY:

529644

show subpopulations

African (AFR)

AF:

0.702

AC:

16473

AN:

23452

American (AMR)

AF:

0.626

AC:

18987

AN:

30352

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

11523

AN:

20796

East Asian (EAS)

AF:

0.733

AC:

26786

AN:

36556

South Asian (SAS)

AF:

0.579

AC:

39879

AN:

68822

European-Finnish (FIN)

AF:

0.448

AC:

23154

AN:

51674

Middle Eastern (MID)

AF:

0.583

AC:

1935

AN:

3320

European-Non Finnish (NFE)

AF:

0.491

AC:

372219

AN:

758836

Other (OTH)

AF:

0.542

AC:

24664

AN:

45534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

12945

25890

38835

51780

64725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9556

19112

28668

38224

47780

<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:

0.571

AC:

86832

AN:

152006

Hom.:

25488

Cov.:

AF XY:

0.570

AC XY:

42314

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.698

AC:

28933

AN:

41452

American (AMR)

AF:

0.581

AC:

8873

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1952

AN:

3470

East Asian (EAS)

AF:

0.729

AC:

3762

AN:

5162

South Asian (SAS)

AF:

0.577

AC:

2775

AN:

4812

European-Finnish (FIN)

AF:

0.437

AC:

4609

AN:

10550

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34214

AN:

67962

Other (OTH)

AF:

0.582

AC:

1227

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1833

3666

5500

7333

9166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.525

Hom.:

7648

Bravo

AF:

0.595

Asia WGS

AF:

0.607

AC:

2113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.3

(source)

DANN

Benign

0.59

PhyloP100

-0.83

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