chr8-143559981-G-GAGGGCAGGGC

Position:

• chr8-143559981-G-GAGGGCAGGGC

Variant summary

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

The NM_024736.7(GSDMD):​c.410+23_410+32dupAGGGCAGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,587,838 control chromosomes in the GnomAD database, including 18,942 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1681 hom., cov: 0)
  • Exomes 𝑓: 0.15 (17261 hom.)
• Consequence: GSDMD NM_024736.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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 (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDMD	NM_024736.7	c.410+23_410+32dupAGGGCAGGGC		intron_variant		ENST00000262580.9	NP_079012.3
GSDMD	NM_001166237.1	c.410+23_410+32dupAGGGCAGGGC		intron_variant			NP_001159709.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMD	ENST00000262580.9	c.410+23_410+32dupAGGGCAGGGC		intron_variant		1	NM_024736.7	ENSP00000262580.4

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22143 AN: 151964 Hom.: 1683 Cov.: 0

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.149 AC: 213237 AN: 1435756 Hom.: 17261 Cov.: 35 AF XY: 0.150 AC XY: 107310 AN XY: 715080

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.186

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.146 AC: 22149 AN: 152082 Hom.: 1681 Cov.: 0 AF XY: 0.145 AC XY: 10763 AN XY: 74338

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.140

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;