17-39917778-T-C

Variant names:

• chr17-39917778-T-C
• rs9303280
• NM_001165958.2:c.-14-448A>G

Variant summary

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

The NM_001388420.1(GSDMB):​c.-462A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 187,632 control chromosomes in the GnomAD database, including 33,078 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 0.59 (27448 hom., cov: 30)
  • Exomes 𝑓: 0.54 (5630 hom.)
• Consequence: GSDMB NM_001388420.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.-14-448A>G		intron_variant	Intron 1 of 10	ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.-14-448A>G		intron_variant	Intron 1 of 10	5	NM_001165958.2	ENSP00000415049.1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89834 AN: 151556 Hom.: 27421 Cov.: 30

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.537 AC: 19308 AN: 35958 Hom.: 5630 Cov.: 0 AF XY: 0.540 AC XY: 10264 AN XY: 19014

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.753

Gnomad4 SAS exome AF: 0.566

Gnomad4 FIN exome AF: 0.442

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.540

GnomAD4 genome AF: 0.593 AC: 89909 AN: 151674 Hom.: 27448 Cov.: 30 AF XY: 0.591 AC XY: 43774 AN XY: 74102

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.602

Alfa AF: 0.414 Hom.: 978

Bravo AF: 0.619

Asia WGS AF: 0.625 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9303280; hg19: chr17-38074031;