17-39912261-T-C

Variant names:

• chr17-39912261-T-C
• rs1011082
• NM_001165958.2:c.407+65A>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+65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 1,191,348 control chromosomes in the GnomAD database, including 166,169 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 0.57 (25488 hom., cov: 31)
  • Exomes 𝑓: 0.52 (140681 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833
• Publications: 23 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 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.407+65A>G		intron	N/A	NP_001159430.1	Q8TAX9-4
	GSDMB	NM_001388420.1		c.407+65A>G		intron	N/A	NP_001375349.1	Q8TAX9-4
	GSDMB	NM_001165959.2		c.407+65A>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.407+65A>G		intron	N/A	ENSP00000415049.1	Q8TAX9-4
	GSDMB	ENST00000360317.7	TSL:1	c.407+65A>G		intron	N/A	ENSP00000353465.3	Q8TAX9-4
	GSDMB	ENST00000394179.5	TSL:1	c.407+65A>G		intron	N/A	ENSP00000377733.2	Q8TAX9-3

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86769 AN: 151888 Hom.: 25474 Cov.: 31

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.581

GnomAD4 exome AF: 0.515 AC: 535620 AN: 1039342 Hom.: 140681 AF XY: 0.517 AC XY: 274014 AN XY: 529644

African (AFR) AF: 0.702 AC: 16473 AN: 23452

American (AMR) AF: 0.626 AC: 18987 AN: 30352

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 11523 AN: 20796

East Asian (EAS) AF: 0.733 AC: 26786 AN: 36556

South Asian (SAS) AF: 0.579 AC: 39879 AN: 68822

European-Finnish (FIN) AF: 0.448 AC: 23154 AN: 51674

Middle Eastern (MID) AF: 0.583 AC: 1935 AN: 3320

European-Non Finnish (NFE) AF: 0.491 AC: 372219 AN: 758836

Other (OTH) AF: 0.542 AC: 24664 AN: 45534

GnomAD4 genome AF: 0.571 AC: 86832 AN: 152006 Hom.: 25488 Cov.: 31 AF XY: 0.570 AC XY: 42314 AN XY: 74292

African (AFR) AF: 0.698 AC: 28933 AN: 41452

American (AMR) AF: 0.581 AC: 8873 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1952 AN: 3470

East Asian (EAS) AF: 0.729 AC: 3762 AN: 5162

South Asian (SAS) AF: 0.577 AC: 2775 AN: 4812

European-Finnish (FIN) AF: 0.437 AC: 4609 AN: 10550

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34214 AN: 67962

Other (OTH) AF: 0.582 AC: 1227 AN: 2108

Alfa AF: 0.525 Hom.: 7648

Bravo AF: 0.595

Asia WGS AF: 0.607 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		-0.83
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: rs1011082; hg19: chr17-38068514;