chr17-39918265-C-T

Position:

• chr17-39918265-C-T

Variant summary

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

The NM_001388420.1(GSDMB):​c.-949G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,876 control chromosomes in the GnomAD database, including 21,058 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 (21055 hom., cov: 31)
  • Exomes 𝑓: 0.56 (3 hom.)
• Consequence: GSDMB NM_001388420.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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]

GSDMB (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMB	NM_001165958.2	c.-15+269G>A		intron_variant		ENST00000418519.6	NP_001159430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMB	ENST00000418519.6	c.-15+269G>A		intron_variant		5	NM_001165958.2	ENSP00000415049.1
GSDMB	ENST00000520542.5	c.-6+269G>A		intron_variant		2		ENSP00000430157.1
GSDMB	ENST00000309481.11	c.-15+269G>A		intron_variant		2		ENSP00000312584.7
GSDMB	ENST00000477054.6	n.1590G>A		non_coding_transcript_exon_variant	1/8	5

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79574 AN: 151742 Hom.: 21055 Cov.: 31

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.563 AC: 9 AN: 16 Hom.: 3 Cov.: 0 AF XY: 0.375 AC XY: 3 AN XY: 8

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.524 AC: 79590 AN: 151860 Hom.: 21055 Cov.: 31 AF XY: 0.525 AC XY: 38942 AN XY: 74230

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.534

Alfa AF: 0.508 Hom.: 19163

Bravo AF: 0.541

Asia WGS AF: 0.583 AC: 2029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.5
DANN	Benign	0.90

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7219923; hg19: chr17-38074518;