dbSNP rs11078927: GSDMB:c.700+24G>A (chr17-39908152-C-T) – 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.700+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,358,612 control chromosomes in the GnomAD database, including 119,376 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 0.35 ( 10770 hom., cov: 30)

Exomes 𝑓: 0.42 ( 108606 hom. )

Consequence

GSDMB
NM_001165958.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.341

Publications

88 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:

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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMB	NM_001165958.2 link	c.700+24G>A		intron_variant	Intron 6 of 10	ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6 link	c.700+24G>A		intron_variant	Intron 6 of 10	5	NM_001165958.2	ENSP00000415049.1

Frequencies

GnomAD3 genomes

AF:

0.349

AC:

52949

AN:

151576

Hom.:

10762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.350

GnomAD2 exomes

AF:

0.399

AC:

62364

AN:

156298

AF XY:

0.404

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.418

Gnomad EAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.522

Gnomad NFE exome

AF:

0.461

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.418

AC:

504775

AN:

1206918

Hom.:

108606

Cov.:

AF XY:

0.418

AC XY:

252822

AN XY:

604168

show subpopulations

African (AFR)

AF:

0.121

AC:

3546

AN:

29186

American (AMR)

AF:

0.335

AC:

11854

AN:

35432

Ashkenazi Jewish (ASJ)

AF:

0.410

AC:

9845

AN:

24038

East Asian (EAS)

AF:

0.263

AC:

9249

AN:

35180

South Asian (SAS)

AF:

0.367

AC:

27796

AN:

75710

European-Finnish (FIN)

AF:

0.509

AC:

24989

AN:

49124

Middle Eastern (MID)

AF:

0.382

AC:

2045

AN:

5354

European-Non Finnish (NFE)

AF:

0.439

AC:

395174

AN:

901034

Other (OTH)

AF:

0.391

AC:

20277

AN:

51860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

11385

22769

34154

45538

56923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10958

21916

32874

43832

54790

<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:

0.349

AC:

52967

AN:

151694

Hom.:

10770

Cov.:

AF XY:

0.352

AC XY:

26110

AN XY:

74076

show subpopulations

African (AFR)

AF:

0.137

AC:

5672

AN:

41386

American (AMR)

AF:

0.372

AC:

5655

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1417

AN:

3468

East Asian (EAS)

AF:

0.269

AC:

1388

AN:

5154

South Asian (SAS)

AF:

0.370

AC:

1781

AN:

4816

European-Finnish (FIN)

AF:

0.519

AC:

5433

AN:

10462

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.445

AC:

30187

AN:

67886

Other (OTH)

AF:

0.347

AC:

732

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1621

3242

4863

6484

8105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.414

Hom.:

40783

Bravo

AF:

0.322

Asia WGS

AF:

0.353

AC:

1228

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.1

(source)

DANN

Benign

0.52

PhyloP100

-0.34

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