17-39917778-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001165958.2(GSDMB):​c.-14-448A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165958.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMB	NM_001165958.2	MANE Select	c.-14-448A>T		intron	N/A	NP_001159430.1
	GSDMB	NM_001388420.1		c.-462A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001375349.1
	GSDMB	NM_001388421.1		c.-462A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001375350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMB	ENST00000418519.6	TSL:5 MANE Select	c.-14-448A>T		intron	N/A	ENSP00000415049.1
	GSDMB	ENST00000477054.6	TSL:5	n.2077A>T		non_coding_transcript_exon	Exon 1 of 8
	GSDMB	ENST00000520542.5	TSL:2	c.-5-457A>T		intron	N/A	ENSP00000430157.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 36096 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 19076

African (AFR) AF: 0.00 AC: 0 AN: 852

American (AMR) AF: 0.00 AC: 0 AN: 3340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 714

East Asian (EAS) AF: 0.00 AC: 0 AN: 2370

South Asian (SAS) AF: 0.00 AC: 0 AN: 4646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 110

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 21186

Other (OTH) AF: 0.00 AC: 0 AN: 1716

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 32360

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.28
PhyloP100		-0.93
PromoterAI		0.047	Neutral

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;