chr17-39917793-G-A

Position:

• chr17-39917793-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001165958.2(GSDMB):​c.-14-463C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 180,966 control chromosomes in the GnomAD database, including 23,226 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 0.50 (19293 hom., cov: 30)
  • Exomes 𝑓: 0.49 (3933 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDMB	NM_001165958.2	c.-14-463C>T		intron_variant		ENST00000418519.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDMB	ENST00000418519.6	c.-14-463C>T		intron_variant		5	NM_001165958.2	P2
GSDMB	ENST00000309481.11	c.-14-463C>T		intron_variant		2		A2
GSDMB	ENST00000520542.5	c.-5-472C>T		intron_variant		2
GSDMB	ENST00000477054.6	n.2062C>T		non_coding_transcript_exon_variant	1/8	5

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76174 AN: 151360 Hom.: 19298 Cov.: 30

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.489 AC: 14419 AN: 29486 Hom.: 3933 Cov.: 0 AF XY: 0.493 AC XY: 7664 AN XY: 15534

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.581

Gnomad4 ASJ exome AF: 0.486

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.404

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.481

GnomAD4 genome AF: 0.503 AC: 76179 AN: 151480 Hom.: 19293 Cov.: 30 AF XY: 0.504 AC XY: 37256 AN XY: 73992

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.727

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.517

Alfa AF: 0.508 Hom.: 3412

Bravo AF: 0.518

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9303281; hg19: chr17-38074046;