Genetic Variant GSDMB:c.-14-463C>T (chr17-39917793-G-A) – 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.-14-463C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 180,966 control chromosomes in the GnomAD database, including 23,226 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 0.50 ( 19293 hom., cov: 30)

Exomes 𝑓: 0.49 ( 3933 hom. )

Consequence

GSDMB
NM_001165958.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.200

Publications

35 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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 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.-14-463C>T	intron	N/A	NP_001159430.1
GSDMB	NM_001388420.1		c.-477C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001375349.1
GSDMB	NM_001388421.1		c.-477C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001375350.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSDMB	ENST00000418519.6	TSL:5 MANE Select	c.-14-463C>T	intron	N/A	ENSP00000415049.1
GSDMB	ENST00000477054.6	TSL:5	n.2062C>T	non_coding_transcript_exon	Exon 1 of 8
GSDMB	ENST00000520542.5	TSL:2	c.-5-472C>T	intron	N/A	ENSP00000430157.1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76174

AN:

151360

Hom.:

19298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.477

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.727

Gnomad SAS

AF:

0.568

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.529

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.516

GnomAD4 exome

AF:

0.489

AC:

14419

AN:

29486

Hom.:

3933

Cov.:

AF XY:

0.493

AC XY:

7664

AN XY:

15534

show subpopulations

African (AFR)

AF:

0.382

AC:

231

AN:

604

American (AMR)

AF:

0.581

AC:

1789

AN:

3080

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

274

AN:

564

East Asian (EAS)

AF:

0.750

AC:

1428

AN:

1904

South Asian (SAS)

AF:

0.524

AC:

1905

AN:

3638

European-Finnish (FIN)

AF:

0.404

AC:

377

AN:

934

Middle Eastern (MID)

AF:

0.477

AC:

AN:

European-Non Finnish (NFE)

AF:

0.446

AC:

7726

AN:

17328

Other (OTH)

AF:

0.481

AC:

648

AN:

1348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

319

638

958

1277

1596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<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:

0.503

AC:

76179

AN:

151480

Hom.:

19293

Cov.:

AF XY:

0.504

AC XY:

37256

AN XY:

73992

show subpopulations

African (AFR)

AF:

0.476

AC:

19641

AN:

41294

American (AMR)

AF:

0.549

AC:

8355

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

1811

AN:

3468

East Asian (EAS)

AF:

0.727

AC:

3735

AN:

5138

South Asian (SAS)

AF:

0.568

AC:

2728

AN:

4802

European-Finnish (FIN)

AF:

0.435

AC:

4546

AN:

10452

Middle Eastern (MID)

AF:

0.534

AC:

156

AN:

292

European-Non Finnish (NFE)

AF:

0.499

AC:

33823

AN:

67816

Other (OTH)

AF:

0.517

AC:

1085

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1876

3753

5629

7506

9382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.507

Hom.:

3510

Bravo

AF:

0.518

Asia WGS

AF:

0.579

AC:

2013

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.9

(source)

DANN

Benign

0.34

PhyloP100

-0.20

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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