Genetic Variant GSDMB:c.-14-257C>A (chr17-39917587-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001388420.1(GSDMB):c.-271C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0016 ( 2 hom., cov: 0)

Exomes 𝑓: 0.00019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GSDMB
NM_001388420.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32

Publications

6 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388420.1. 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.-14-257C>A	intron	N/A	NP_001159430.1	Q8TAX9-4
GSDMB	NM_001388420.1		c.-271C>A	5_prime_UTR	Exon 1 of 10	NP_001375349.1	Q8TAX9-4
GSDMB	NM_001388421.1		c.-271C>A	5_prime_UTR	Exon 1 of 9	NP_001375350.1	Q8TAX9-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GSDMB	ENST00000418519.6	TSL:5 MANE Select	c.-14-257C>A	intron	N/A	ENSP00000415049.1	Q8TAX9-4
GSDMB	ENST00000901434.1		c.-271C>A	5_prime_UTR	Exon 1 of 9	ENSP00000571493.1
GSDMB	ENST00000959630.1		c.-271C>A	5_prime_UTR	Exon 1 of 6	ENSP00000629689.1

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

AN:

35134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00940

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000331

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000511

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000193

AC:

AN:

67430

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

35262

show subpopulations

African (AFR)

AF:

0.00795

AC:

AN:

1132

American (AMR)

AF:

0.000470

AC:

AN:

2126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1710

East Asian (EAS)

AF:

0.00

AC:

AN:

966

South Asian (SAS)

AF:

0.00

AC:

AN:

7902

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4540

Middle Eastern (MID)

AF:

0.00

AC:

AN:

220

European-Non Finnish (NFE)

AF:

0.0000664

AC:

AN:

45194

Other (OTH)

AF:

0.00

AC:

AN:

3640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00159

AC:

AN:

35134

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

AN XY:

17244

show subpopulations

African (AFR)

AF:

0.00940

AC:

AN:

5742

American (AMR)

AF:

0.000331

AC:

AN:

3024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

768

East Asian (EAS)

AF:

0.00

AC:

AN:

412

South Asian (SAS)

AF:

0.00

AC:

AN:

980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0000511

AC:

AN:

19586

Other (OTH)

AF:

0.00

AC:

AN:

440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.3

(source)

DANN

Benign

0.52

PhyloP100

-1.3

PromoterAI

0.013

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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