chr17-39911790-T-C

Variant names:

• chr17-39911790-T-C
• rs869402
• NM_001165958.2:c.407+536A>G

Variant summary

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

The NM_001165958.2(GSDMB):​c.407+536A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,922 control chromosomes in the GnomAD database, including 28,691 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 (28691 hom., cov: 31)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 37 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.407+536A>G		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.407+536A>G		intron_variant	Intron 3 of 10	5	NM_001165958.2	ENSP00000415049.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91119 AN: 151804 Hom.: 28648 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.600 AC: 91209 AN: 151922 Hom.: 28691 Cov.: 31 AF XY: 0.599 AC XY: 44447 AN XY: 74216

African (AFR) AF: 0.797 AC: 33059 AN: 41472

American (AMR) AF: 0.592 AC: 9029 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1951 AN: 3466

East Asian (EAS) AF: 0.730 AC: 3774 AN: 5172

South Asian (SAS) AF: 0.578 AC: 2790 AN: 4826

European-Finnish (FIN) AF: 0.440 AC: 4612 AN: 10490

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34234 AN: 67924

Other (OTH) AF: 0.602 AC: 1271 AN: 2110

Alfa AF: 0.593 Hom.: 6767

Bravo AF: 0.628

Asia WGS AF: 0.626 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.88
PhyloP100		-0.20
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: rs869402; hg19: chr17-38068043;