chr17-39909987-T-C

Variant names:

• chr17-39909987-T-C
• rs2290400
• NM_001165958.2:c.408-63A>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.408-63A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,265,582 control chromosomes in the GnomAD database, including 150,310 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 0.48 (17511 hom., cov: 32)
  • Exomes 𝑓: 0.48 (132799 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 176 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165958.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMB	NM_001165958.2	MANE Select	c.408-63A>G		intron	N/A	NP_001159430.1	Q8TAX9-4
	GSDMB	NM_001388420.1		c.408-63A>G		intron	N/A	NP_001375349.1	Q8TAX9-4
	GSDMB	NM_001165959.2		c.408-63A>G		intron	N/A	NP_001159431.1	Q8TAX9-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMB	ENST00000418519.6	TSL:5 MANE Select	c.408-63A>G		intron	N/A	ENSP00000415049.1	Q8TAX9-4
	GSDMB	ENST00000360317.7	TSL:1	c.408-63A>G		intron	N/A	ENSP00000353465.3	Q8TAX9-4
	GSDMB	ENST00000394179.5	TSL:1	c.408-63A>G		intron	N/A	ENSP00000377733.2	Q8TAX9-3

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72467 AN: 151890 Hom.: 17464 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.484 AC: 539188 AN: 1113574 Hom.: 132799 AF XY: 0.482 AC XY: 272600 AN XY: 565578

African (AFR) AF: 0.483 AC: 12442 AN: 25748

American (AMR) AF: 0.382 AC: 14210 AN: 37178

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 10318 AN: 21902

East Asian (EAS) AF: 0.266 AC: 10080 AN: 37872

South Asian (SAS) AF: 0.425 AC: 31622 AN: 74450

European-Finnish (FIN) AF: 0.551 AC: 28407 AN: 51588

Middle Eastern (MID) AF: 0.512 AC: 2463 AN: 4814

European-Non Finnish (NFE) AF: 0.501 AC: 406779 AN: 811780

Other (OTH) AF: 0.474 AC: 22867 AN: 48242

GnomAD4 genome AF: 0.477 AC: 72575 AN: 152008 Hom.: 17511 Cov.: 32 AF XY: 0.477 AC XY: 35435 AN XY: 74294

African (AFR) AF: 0.475 AC: 19664 AN: 41440

American (AMR) AF: 0.439 AC: 6694 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1617 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1422 AN: 5176

South Asian (SAS) AF: 0.429 AC: 2068 AN: 4816

European-Finnish (FIN) AF: 0.561 AC: 5926 AN: 10572

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33465 AN: 67968

Other (OTH) AF: 0.464 AC: 975 AN: 2100

Alfa AF: 0.485 Hom.: 76533

Bravo AF: 0.461

Asia WGS AF: 0.417 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.71
DANN	Benign	0.35
PhyloP100		-1.2
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: rs2290400; hg19: chr17-38066240; COSMIC: COSV58783257; COSMIC: COSV58783257;