rs7216389

Positions:

• chr17-39913696-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.236-1199G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,028 control chromosomes in the GnomAD database, including 28,368 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 0.60 (28368 hom., cov: 31)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23

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 (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.236-1199G>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.236-1199G>A		intron_variant		5	NM_001165958.2	ENSP00000415049	P2

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90717 AN: 151910 Hom.: 28329 Cov.: 31

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.597

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.597 AC: 90802 AN: 152028 Hom.: 28368 Cov.: 31 AF XY: 0.595 AC XY: 44237 AN XY: 74290

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.599

Alfa AF: 0.524 Hom.: 46166

Bravo AF: 0.625

Asia WGS AF: 0.625 AC: 2176 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	0.012
DANN	Benign	0.66

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: rs7216389; hg19: chr17-38069949; COSMIC: COSV58782744; COSMIC: COSV58782744;