chr17-39909987-T-A

Variant names:

• chr17-39909987-T-A
• rs2290400
• NM_001165958.2:c.408-63A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001165958.2(GSDMB):​c.408-63A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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>T		intron	N/A	NP_001159430.1	Q8TAX9-4
	GSDMB	NM_001388420.1		c.408-63A>T		intron	N/A	NP_001375349.1	Q8TAX9-4
	GSDMB	NM_001165959.2		c.408-63A>T		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>T		intron	N/A	ENSP00000415049.1	Q8TAX9-4
	GSDMB	ENST00000360317.7	TSL:1	c.408-63A>T		intron	N/A	ENSP00000353465.3	Q8TAX9-4
	GSDMB	ENST00000394179.5	TSL:1	c.408-63A>T		intron	N/A	ENSP00000377733.2	Q8TAX9-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1116878 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 567204

African (AFR) AF: 0.00 AC: 0 AN: 25816

American (AMR) AF: 0.00 AC: 0 AN: 37226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21944

East Asian (EAS) AF: 0.00 AC: 0 AN: 37912

South Asian (SAS) AF: 0.00 AC: 0 AN: 74586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4838

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 814540

Other (OTH) AF: 0.00 AC: 0 AN: 48364

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.49
PhyloP100		-1.2

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;