rs11078927

Positions:

• chr17-39908152-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001165958.2(GSDMB):​c.700+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,358,612 control chromosomes in the GnomAD database, including 119,376 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 0.35 (10770 hom., cov: 30)
  • Exomes 𝑓: 0.42 (108606 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.700+24G>A		intron_variant		ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.700+24G>A		intron_variant		5	NM_001165958.2	ENSP00000415049.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52949 AN: 151576 Hom.: 10762 Cov.: 30

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.350

GnomAD3 exomes AF: 0.399 AC: 62364 AN: 156298 Hom.: 13202 AF XY: 0.404 AC XY: 33440 AN XY: 82838

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.418

Gnomad EAS exome AF: 0.254

Gnomad SAS exome AF: 0.373

Gnomad FIN exome AF: 0.522

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.418 AC: 504775 AN: 1206918 Hom.: 108606 Cov.: 18 AF XY: 0.418 AC XY: 252822 AN XY: 604168

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.439

Gnomad4 OTH exome AF: 0.391

GnomAD4 genome AF: 0.349 AC: 52967 AN: 151694 Hom.: 10770 Cov.: 30 AF XY: 0.352 AC XY: 26110 AN XY: 74076

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.347

Alfa AF: 0.428 Hom.: 16341

Bravo AF: 0.322

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.52

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

LitVar

Other links and lift over

dbSNP: rs11078927; hg19: chr17-38064405; COSMIC: COSV58780115; COSMIC: COSV58780115;