17-39917587-G-C

Position:

• chr17-39917587-G-C

Variant summary

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

The NM_001165958.2(GSDMB):​c.-14-257C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.18 (213 hom., cov: 0)
  • Exomes 𝑓: 0.12 (214 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.-14-257C>G		intron_variant		ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.-14-257C>G		intron_variant		5	NM_001165958.2	ENSP00000415049	P2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 6118 AN: 34888 Hom.: 213 Cov.: 0

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.00971

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0652

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.187

GnomAD4 exome AF: 0.121 AC: 8164 AN: 67258 Hom.: 214 Cov.: 0 AF XY: 0.118 AC XY: 4151 AN XY: 35172

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.0796

Gnomad4 EAS exome AF: 0.00311

Gnomad4 SAS exome AF: 0.0932

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.175 AC: 6119 AN: 34912 Hom.: 213 Cov.: 0 AF XY: 0.169 AC XY: 2901 AN XY: 17134

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0951

Gnomad4 EAS AF: 0.00971

Gnomad4 SAS AF: 0.0890

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.187

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	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs77749396; hg19: chr17-38073840;