17-39917778-T-C

Variant names:

• chr17-39917778-T-C
• rs9303280
• NM_001165958.2:c.-14-448A>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.-14-448A>G variant causes a intron 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_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 44 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=-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

African (AFR) AF: 0.750 AC: 639 AN: 852

American (AMR) AF: 0.622 AC: 2072 AN: 3332

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 405 AN: 708

East Asian (EAS) AF: 0.753 AC: 1776 AN: 2360

South Asian (SAS) AF: 0.566 AC: 2620 AN: 4632

European-Finnish (FIN) AF: 0.442 AC: 513 AN: 1160

Middle Eastern (MID) AF: 0.682 AC: 75 AN: 110

European-Non Finnish (NFE) AF: 0.488 AC: 10285 AN: 21096

Other (OTH) AF: 0.540 AC: 923 AN: 1708

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

African (AFR) AF: 0.740 AC: 30640 AN: 41392

American (AMR) AF: 0.596 AC: 9079 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3468

East Asian (EAS) AF: 0.728 AC: 3735 AN: 5130

South Asian (SAS) AF: 0.581 AC: 2788 AN: 4802

European-Finnish (FIN) AF: 0.448 AC: 4706 AN: 10502

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35171 AN: 67840

Other (OTH) AF: 0.602 AC: 1266 AN: 2104

Alfa AF: 0.547 Hom.: 32360

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
PhyloP100		-0.93
PromoterAI		0.033	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9303280; hg19: chr17-38074031;