17-39912261-T-C

Position:

• chr17-39912261-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDMB	NM_001165958.2	c.407+65A>G		intron_variant		ENST00000418519.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDMB	ENST00000418519.6	c.407+65A>G		intron_variant		5	NM_001165958.2	P2

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

Gnomad4 AFR exome AF: 0.702

Gnomad4 AMR exome AF: 0.626

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.733

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.491

Gnomad4 OTH exome AF: 0.542

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

Gnomad4 AFR AF: 0.698

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.729

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.582

Alfa AF: 0.513 Hom.: 5633

Bravo AF: 0.595

Asia WGS AF: 0.607 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1011082; hg19: chr17-38068514;