rs2290400

Positions:

• chr17-39909987-T-C

Variant summary

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

The NM_001165958.2(GSDMB):​c.408-63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,265,582 control chromosomes in the GnomAD database, including 150,310 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 0.48 (17511 hom., cov: 32)
  • Exomes 𝑓: 0.48 (132799 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.408-63A>G		intron_variant		ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.408-63A>G		intron_variant		5	NM_001165958.2	ENSP00000415049	P2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72467 AN: 151890 Hom.: 17464 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.484 AC: 539188 AN: 1113574 Hom.: 132799 AF XY: 0.482 AC XY: 272600 AN XY: 565578

Gnomad4 AFR exome AF: 0.483

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.471

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.501

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.477 AC: 72575 AN: 152008 Hom.: 17511 Cov.: 32 AF XY: 0.477 AC XY: 35435 AN XY: 74294

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.464

Alfa AF: 0.488 Hom.: 38886

Bravo AF: 0.461

Asia WGS AF: 0.417 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.71
DANN	Benign	0.35

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: rs2290400; hg19: chr17-38066240; COSMIC: COSV58783257; COSMIC: COSV58783257;