chr17-39919173-G-A

Variant names:

• chr17-39919173-G-A
• rs7224129
• ENST00000477054.6:n.682C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000477054.6(GSDMB):​n.682C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,086 control chromosomes in the GnomAD database, including 21,047 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 0.52 (21026 hom., cov: 31)
  • Exomes 𝑓: 0.46 (21 hom.)
• Consequence: GSDMB ENST00000477054.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65
• Publications: 37 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000477054.6	n.682C>T		non_coding_transcript_exon_variant	Exon 1 of 8	5

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79525 AN: 151778 Hom.: 21026 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.458 AC: 87 AN: 190 Hom.: 21 Cov.: 0 AF XY: 0.433 AC XY: 58 AN XY: 134

African (AFR) AF: 0.400 AC: 4 AN: 10

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.449 AC: 70 AN: 156

Other (OTH) AF: 0.500 AC: 4 AN: 8

GnomAD4 genome AF: 0.524 AC: 79540 AN: 151896 Hom.: 21026 Cov.: 31 AF XY: 0.524 AC XY: 38910 AN XY: 74228

African (AFR) AF: 0.548 AC: 22676 AN: 41388

American (AMR) AF: 0.556 AC: 8490 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1813 AN: 3470

East Asian (EAS) AF: 0.719 AC: 3697 AN: 5144

South Asian (SAS) AF: 0.569 AC: 2739 AN: 4814

European-Finnish (FIN) AF: 0.436 AC: 4597 AN: 10546

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33948 AN: 67964

Other (OTH) AF: 0.533 AC: 1123 AN: 2108

Alfa AF: 0.508 Hom.: 75972

Bravo AF: 0.541

Asia WGS AF: 0.581 AC: 2020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.70
PhyloP100		2.6

Splicing

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

Other links and lift over

dbSNP: rs7224129; hg19: chr17-38075426;