Genetic Variant GSDMB:c.408-90C>A (chr17-39910014-G-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.408-90C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 990,980 control chromosomes in the GnomAD database, including 110,398 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 0.42 ( 14196 hom., cov: 32)

Exomes 𝑓: 0.47 ( 96202 hom. )

Consequence

GSDMB
NM_001165958.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.679

Publications

52 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=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165958.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSDMB	NM_001165958.2	MANE Select	c.408-90C>A	intron	N/A	NP_001159430.1
GSDMB	NM_001388420.1		c.408-90C>A	intron	N/A	NP_001375349.1
GSDMB	NM_001165959.2		c.408-90C>A	intron	N/A	NP_001159431.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSDMB	ENST00000418519.6	TSL:5 MANE Select	c.408-90C>A	intron	N/A	ENSP00000415049.1
GSDMB	ENST00000360317.7	TSL:1	c.408-90C>A	intron	N/A	ENSP00000353465.3
GSDMB	ENST00000394179.5	TSL:1	c.408-90C>A	intron	N/A	ENSP00000377733.2

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64052

AN:

151920

Hom.:

14182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.673

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.272

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.413

GnomAD4 exome

AF:

0.473

AC:

396795

AN:

838942

Hom.:

96202

AF XY:

0.471

AC XY:

203963

AN XY:

433494

show subpopulations

African (AFR)

AF:

0.296

AC:

5992

AN:

20248

American (AMR)

AF:

0.359

AC:

11101

AN:

30910

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

7927

AN:

17938

East Asian (EAS)

AF:

0.266

AC:

9746

AN:

36698

South Asian (SAS)

AF:

0.408

AC:

25192

AN:

61744

European-Finnish (FIN)

AF:

0.549

AC:

26571

AN:

48406

Middle Eastern (MID)

AF:

0.413

AC:

1597

AN:

3870

European-Non Finnish (NFE)

AF:

0.502

AC:

291115

AN:

580302

Other (OTH)

AF:

0.452

AC:

17554

AN:

38826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

10161

20323

30484

40646

50807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6036

12072

18108

24144

30180

<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:

0.422

AC:

64098

AN:

152038

Hom.:

14196

Cov.:

AF XY:

0.423

AC XY:

31441

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.294

AC:

12204

AN:

41462

American (AMR)

AF:

0.410

AC:

6267

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1519

AN:

3470

East Asian (EAS)

AF:

0.272

AC:

1407

AN:

5166

South Asian (SAS)

AF:

0.413

AC:

1993

AN:

4820

European-Finnish (FIN)

AF:

0.561

AC:

5920

AN:

10558

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.488

AC:

33202

AN:

67972

Other (OTH)

AF:

0.412

AC:

870

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1802

3604

5407

7209

9011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.375

Hom.:

5759

Bravo

AF:

0.397

Asia WGS

AF:

0.389

AC:

1352

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.70

(source)

DANN

Benign

0.60

PhyloP100

-0.68

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