Genetic Variant GSDMB:c.-1447A>G (chr17-39918763-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 ENST00000901434.1(GSDMB):c.-1447A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 133,892 control chromosomes in the GnomAD database, including 20,013 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 ( 20013 hom., cov: 26)

Exomes 𝑓: 0.58 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

GSDMB
ENST00000901434.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.362

Publications

10 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000901434.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSDMB	NM_001165958.2	MANE Select	c.-244A>G	upstream_gene	N/A	NP_001159430.1	Q8TAX9-4
GSDMB	NM_001388420.1		c.-1447A>G	upstream_gene	N/A	NP_001375349.1	Q8TAX9-4
GSDMB	NM_001165959.2		c.-235A>G	upstream_gene	N/A	NP_001159431.1	Q8TAX9-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSDMB	ENST00000901434.1		c.-1447A>G	5_prime_UTR	Exon 1 of 9	ENSP00000571493.1
GSDMB	ENST00000477054.6	TSL:5	n.1092A>G	non_coding_transcript_exon	Exon 1 of 8
GSDMB	ENST00000418519.6	TSL:5 MANE Select	c.-244A>G	upstream_gene	N/A	ENSP00000415049.1	Q8TAX9-4

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

76960

AN:

133872

Hom.:

20014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.658

Gnomad AMI

AF:

0.379

Gnomad AMR

AF:

0.592

Gnomad ASJ

AF:

0.565

Gnomad EAS

AF:

0.730

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.596

Gnomad NFE

AF:

0.531

Gnomad OTH

AF:

0.595

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.583

AC:

AN:

Hom.:

Cov.:

AF XY:

0.600

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.714

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.575

AC:

76965

AN:

133892

Hom.:

20013

Cov.:

AF XY:

0.574

AC XY:

37529

AN XY:

65340

show subpopulations

African (AFR)

AF:

0.658

AC:

21605

AN:

32844

American (AMR)

AF:

0.591

AC:

8276

AN:

14006

Ashkenazi Jewish (ASJ)

AF:

0.565

AC:

1809

AN:

3202

East Asian (EAS)

AF:

0.729

AC:

3659

AN:

5016

South Asian (SAS)

AF:

0.589

AC:

2651

AN:

4500

European-Finnish (FIN)

AF:

0.472

AC:

4113

AN:

8716

Middle Eastern (MID)

AF:

0.600

AC:

156

AN:

260

European-Non Finnish (NFE)

AF:

0.531

AC:

33308

AN:

62734

Other (OTH)

AF:

0.596

AC:

1092

AN:

1832

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1786

3573

5359

7146

8932

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.547

Hom.:

3263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.26

PhyloP100

-0.36

PromoterAI

0.035

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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