rs4795400

Variant names:

• chr17-39910767-C-T
• rs4795400
• NM_001165958.2:c.408-843G>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.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
• Publications: 47 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=-0.77).
• 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 rank	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.408-843G>A		intron_variant	Intron 3 of 10	ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.408-843G>A		intron_variant	Intron 3 of 10	5	NM_001165958.2	ENSP00000415049.1

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

African (AFR) AF: 0.161 AC: 6688 AN: 41496

American (AMR) AF: 0.375 AC: 5729 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1445 AN: 3470

East Asian (EAS) AF: 0.270 AC: 1396 AN: 5170

South Asian (SAS) AF: 0.396 AC: 1905 AN: 4814

European-Finnish (FIN) AF: 0.521 AC: 5496 AN: 10550

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30291 AN: 67934

Other (OTH) AF: 0.356 AC: 750 AN: 2108

Alfa AF: 0.372 Hom.: 3722

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
PhyloP100		-0.80
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: rs4795400; hg19: chr17-38067020;