chr8-143559981-G-GAGGGCAGGGC

Variant names:

• chr8-143559981-G-GAGGGCAGGGC
• rs59118283
• NM_024736.7:c.410+23_410+32dupAGGGCAGGGC

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024736.7. 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
	GSDMD	NM_024736.7	MANE Select	c.410+23_410+32dupAGGGCAGGGC		intron	N/A	NP_079012.3
	GSDMD	NM_001166237.1		c.410+23_410+32dupAGGGCAGGGC		intron	N/A	NP_001159709.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMD	ENST00000262580.9	TSL:1 MANE Select	c.410+23_410+32dupAGGGCAGGGC		intron	N/A	ENSP00000262580.4
	GSDMD	ENST00000533063.5	TSL:1	c.554+23_554+32dupAGGGCAGGGC		intron	N/A	ENSP00000433958.1
	GSDMD	ENST00000524846.5	TSL:2	n.1080_1089dupAGGGCAGGGC		non_coding_transcript_exon	Exon 2 of 6

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

African (AFR) AF: 0.157 AC: 5162 AN: 32804

American (AMR) AF: 0.186 AC: 8091 AN: 43562

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 4439 AN: 25710

East Asian (EAS) AF: 0.193 AC: 7598 AN: 39422

South Asian (SAS) AF: 0.205 AC: 17342 AN: 84664

European-Finnish (FIN) AF: 0.119 AC: 6191 AN: 51820

Middle Eastern (MID) AF: 0.159 AC: 907 AN: 5696

European-Non Finnish (NFE) AF: 0.141 AC: 154394 AN: 1092636

Other (OTH) AF: 0.153 AC: 9113 AN: 59442

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

African (AFR) AF: 0.150 AC: 6217 AN: 41450

American (AMR) AF: 0.125 AC: 1912 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3470

East Asian (EAS) AF: 0.205 AC: 1058 AN: 5172

South Asian (SAS) AF: 0.191 AC: 919 AN: 4820

European-Finnish (FIN) AF: 0.116 AC: 1229 AN: 10586

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9752 AN: 67966

Other (OTH) AF: 0.140 AC: 296 AN: 2110

Alfa AF: 0.113 Hom.: 183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34
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: rs59118283; hg19: chr8-144642151; COSMIC: COSV52796367; COSMIC: COSV52796367;