17-39913818-C-T

Variant names:

• chr17-39913818-C-T
• rs7216558
• NM_001165958.2:c.236-1321G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001165958.2(GSDMB):​c.236-1321G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,962 control chromosomes in the GnomAD database, including 21,089 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 (21089 hom., cov: 31)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.236-1321G>A		intron_variant	Intron 2 of 10	ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.236-1321G>A		intron_variant	Intron 2 of 10	5	NM_001165958.2	ENSP00000415049.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79650 AN: 151844 Hom.: 21089 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.524 AC: 79666 AN: 151962 Hom.: 21089 Cov.: 31 AF XY: 0.525 AC XY: 38963 AN XY: 74244

African (AFR) AF: 0.548 AC: 22721 AN: 41424

American (AMR) AF: 0.556 AC: 8491 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1810 AN: 3466

East Asian (EAS) AF: 0.729 AC: 3758 AN: 5154

South Asian (SAS) AF: 0.568 AC: 2740 AN: 4828

European-Finnish (FIN) AF: 0.437 AC: 4612 AN: 10564

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33956 AN: 67952

Other (OTH) AF: 0.533 AC: 1122 AN: 2106

Alfa AF: 0.542 Hom.: 4085

Bravo AF: 0.541

Asia WGS AF: 0.583 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7216558; hg19: chr17-38070071;