rs7224129

Positions:

• chr17-39919173-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000477054.6	n.682C>T		non_coding_transcript_exon_variant	1/8	5

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79525 AN: 151778 Hom.: 21026 Cov.: 31

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: 87 AN: 190 Hom.: 21 Cov.: 0 AF XY: 0.433 AC XY: 58 AN XY: 134

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.524 AC: 79540 AN: 151896 Hom.: 21026 Cov.: 31 AF XY: 0.524 AC XY: 38910 AN XY: 74228

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.533

Alfa AF: 0.505 Hom.: 32804

Bravo AF: 0.541

Asia WGS AF: 0.581 AC: 2020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7224129; hg19: chr17-38075426;