8-143559981-GAGGGCAGGGC-GAGGGC

Variant names:

• chr8-143559981-GAGGGC-G
• rs59118283
• NM_024736.7:c.410+28_410+32delAGGGC

Variant summary

Our verdict is Benign. The variant received -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
• 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 (AFR) allele frequency at 95% confidence interval = 0.171 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+28_410+32delAGGGC		intron	N/A	NP_079012.3
	GSDMD	NM_001166237.1		c.410+28_410+32delAGGGC		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+28_410+32delAGGGC		intron	N/A	ENSP00000262580.4
	GSDMD	ENST00000533063.5	TSL:1	c.554+28_554+32delAGGGC		intron	N/A	ENSP00000433958.1
	GSDMD	ENST00000524846.5	TSL:2	n.1085_1089delAGGGC		non_coding_transcript_exon	Exon 2 of 6

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

African (AFR) AF: 0.184 AC: 6026 AN: 32766

American (AMR) AF: 0.0131 AC: 571 AN: 43590

Ashkenazi Jewish (ASJ) AF: 0.0000389 AC: 1 AN: 25712

East Asian (EAS) AF: 0.0000761 AC: 3 AN: 39434

South Asian (SAS) AF: 0.000437 AC: 37 AN: 84706

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51834

Middle Eastern (MID) AF: 0.0107 AC: 61 AN: 5698

European-Non Finnish (NFE) AF: 0.000642 AC: 701 AN: 1092730

Other (OTH) AF: 0.0129 AC: 768 AN: 59438

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

African (AFR) AF: 0.174 AC: 7216 AN: 41444

American (AMR) AF: 0.0258 AC: 395 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000780 AC: 53 AN: 67974

Other (OTH) AF: 0.0417 AC: 88 AN: 2110

Alfa AF: 0.00313 Hom.: 183

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.48
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;