dbSNP rs7224129: GSDMB:n.682C>T (chr17-39919173-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 ENST00000477054.6(GSDMB):n.682C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,086 control chromosomes in the GnomAD database, including 21,047 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 0.52 ( 21026 hom., cov: 31)

Exomes 𝑓: 0.46 ( 21 hom. )

Consequence

GSDMB
ENST00000477054.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.65

Publications

37 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000477054.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMB	ENST00000477054.6	TSL:5	n.682C>T		non_coding_transcript_exon	Exon 1 of 8
	GSDMB	ENST00000901434.1		c.-1857C>T		upstream_gene	N/A	ENSP00000571493.1

Frequencies

GnomAD3 genomes

AF:

0.524

AC:

79525

AN:

151778

Hom.:

21026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.549

Gnomad AMI

AF:

0.329

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.522

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.532

GnomAD4 exome

AF:

0.458

AC:

AN:

190

Hom.:

Cov.:

AF XY:

0.433

AC XY:

AN XY:

134

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.449

AC:

AN:

156

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.524

AC:

79540

AN:

151896

Hom.:

21026

Cov.:

AF XY:

0.524

AC XY:

38910

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.548

AC:

22676

AN:

41388

American (AMR)

AF:

0.556

AC:

8490

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.522

AC:

1813

AN:

3470

East Asian (EAS)

AF:

0.719

AC:

3697

AN:

5144

South Asian (SAS)

AF:

0.569

AC:

2739

AN:

4814

European-Finnish (FIN)

AF:

0.436

AC:

4597

AN:

10546

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.499

AC:

33948

AN:

67964

Other (OTH)

AF:

0.533

AC:

1123

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1933

3866

5798

7731

9664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.508

Hom.:

75972

Bravo

AF:

0.541

Asia WGS

AF:

0.581

AC:

2020

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

2.6

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