rs4795400

chr17-39910767-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.408-843G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,008 control chromosomes in the GnomAD database, including 11,097 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 0.36 (11097 hom., cov: 31)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDMB	NM_001165958.2	c.408-843G>A		intron_variant		ENST00000418519.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDMB	ENST00000418519.6	c.408-843G>A		intron_variant		5	NM_001165958.2	P2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54373 AN: 151890 Hom.: 11086 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.358 AC: 54403 AN: 152008 Hom.: 11097 Cov.: 31 AF XY: 0.361 AC XY: 26857 AN XY: 74300

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.356

Alfa AF: 0.386 Hom.: 3525

Bravo AF: 0.331

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	7.8
Dann	Benign	0.81

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: rs4795400; hg19: chr17-38067020;