rs59118283

Positions:

• chr8-143559981-GAGGGC-G
• chr8-143559981-GAGGGC-GAGGGCAGGGC
• chr8-143559981-GAGGGC-GAGGGCAGGGCAGGGC
• chr8-143559981-GAGGGC-GAGGGCAGGGCAGGGCAGGGC
• chr8-143559981-GAGGGC-GAGGGCAGGGCAGGGCAGGGCAGGGC
• chr8-143559981-GAGGGC-GAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC
• chr8-143559981-GAGGGC-GAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC
• chr8-143559981-GAGGGC-GAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGCAGGGC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_024736.7(GSDMD):​c.410+28_410+32delAGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,587,998 control chromosomes in the GnomAD database, including 1,241 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.051 (647 hom., cov: 0)
  • Exomes 𝑓: 0.0057 (594 hom.)
• Consequence: GSDMD NM_024736.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478

Genes affected

GSDMD (HGNC:25697): (gasdermin D) Gasdermin D is a member of the gasdermin family. Members of this family appear to play a role in regulation of epithelial proliferation. Gasdermin D has been suggested to act as a tumor suppressor. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2009]

GSDMD (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMD	NM_024736.7	c.410+28_410+32delAGGGC		intron_variant		ENST00000262580.9	NP_079012.3
GSDMD	NM_001166237.1	c.410+28_410+32delAGGGC		intron_variant			NP_001159709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMD	ENST00000262580.9	c.410+28_410+32delAGGGC		intron_variant		1	NM_024736.7	ENSP00000262580.4

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7743 AN: 151972 Hom.: 645 Cov.: 0

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000780

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.00569 AC: 8169 AN: 1435908 Hom.: 594 AF XY: 0.00491 AC XY: 3515 AN XY: 715202

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.0131

Gnomad4 ASJ exome AF: 0.0000389

Gnomad4 EAS exome AF: 0.0000761

Gnomad4 SAS exome AF: 0.000437

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.000642

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.0510 AC: 7762 AN: 152090 Hom.: 647 Cov.: 0 AF XY: 0.0492 AC XY: 3661 AN XY: 74344

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000780

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.00313 Hom.: 183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59118283; hg19: chr8-144642151;