NM_001165958.2:c.-14-463C>T

Variant names:

• chr17-39917793-G-A
• rs9303281
• NM_001165958.2:c.-14-463C>T

Variant summary

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

The NM_001165958.2(GSDMB):​c.-14-463C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 180,966 control chromosomes in the GnomAD database, including 23,226 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 0.50 (19293 hom., cov: 30)
  • Exomes 𝑓: 0.49 (3933 hom.)
• Consequence: GSDMB NM_001165958.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 35 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

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.-14-463C>T		intron	N/A	NP_001159430.1
	GSDMB	NM_001388420.1		c.-477C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001375349.1
	GSDMB	NM_001388421.1		c.-477C>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.-14-463C>T		intron	N/A	ENSP00000415049.1
	GSDMB	ENST00000477054.6	TSL:5	n.2062C>T		non_coding_transcript_exon	Exon 1 of 8
	GSDMB	ENST00000520542.5	TSL:2	c.-5-472C>T		intron	N/A	ENSP00000430157.1

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76174 AN: 151360 Hom.: 19298 Cov.: 30

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.529

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.489 AC: 14419 AN: 29486 Hom.: 3933 Cov.: 0 AF XY: 0.493 AC XY: 7664 AN XY: 15534

African (AFR) AF: 0.382 AC: 231 AN: 604

American (AMR) AF: 0.581 AC: 1789 AN: 3080

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 274 AN: 564

East Asian (EAS) AF: 0.750 AC: 1428 AN: 1904

South Asian (SAS) AF: 0.524 AC: 1905 AN: 3638

European-Finnish (FIN) AF: 0.404 AC: 377 AN: 934

Middle Eastern (MID) AF: 0.477 AC: 41 AN: 86

European-Non Finnish (NFE) AF: 0.446 AC: 7726 AN: 17328

Other (OTH) AF: 0.481 AC: 648 AN: 1348

GnomAD4 genome AF: 0.503 AC: 76179 AN: 151480 Hom.: 19293 Cov.: 30 AF XY: 0.504 AC XY: 37256 AN XY: 73992

African (AFR) AF: 0.476 AC: 19641 AN: 41294

American (AMR) AF: 0.549 AC: 8355 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1811 AN: 3468

East Asian (EAS) AF: 0.727 AC: 3735 AN: 5138

South Asian (SAS) AF: 0.568 AC: 2728 AN: 4802

European-Finnish (FIN) AF: 0.435 AC: 4546 AN: 10452

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33823 AN: 67816

Other (OTH) AF: 0.517 AC: 1085 AN: 2098

Alfa AF: 0.507 Hom.: 3510

Bravo AF: 0.518

Asia WGS AF: 0.579 AC: 2013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		-0.20
PromoterAI		-0.015	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: rs9303281; hg19: chr17-38074046;