8-143559981-G-GAGGGC

Position:

• chr8-143559981-G-GAGGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024736.7(GSDMD):​c.410+28_410+32dupAGGGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 1,587,794 control chromosomes in the GnomAD database, including 6,409 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.093 (672 hom., cov: 0)
  • Exomes 𝑓: 0.085 (5737 hom.)
• Consequence: GSDMD NM_024736.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 8-143559981-G-GAGGGC is Benign according to our data. Variant chr8-143559981-G-GAGGGC is described in ClinVar as [Benign]. Clinvar id is 402914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 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+32dupAGGGC		intron_variant		ENST00000262580.9	NP_079012.3
GSDMD	NM_001166237.1	c.410+28_410+32dupAGGGC		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+32dupAGGGC		intron_variant		1	NM_024736.7	ENSP00000262580.4

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14143 AN: 151958 Hom.: 668 Cov.: 0

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0650

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0902

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0809

Gnomad OTH AF: 0.0877

GnomAD4 exome AF: 0.0847 AC: 121662 AN: 1435718 Hom.: 5737 Cov.: 35 AF XY: 0.0869 AC XY: 62140 AN XY: 715088

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0493

Gnomad4 ASJ exome AF: 0.0841

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.0882

Gnomad4 NFE exome AF: 0.0788

Gnomad4 OTH exome AF: 0.0893

GnomAD4 genome AF: 0.0931 AC: 14162 AN: 152076 Hom.: 672 Cov.: 0 AF XY: 0.0948 AC XY: 7050 AN XY: 74348

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0649

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.0902

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.0878

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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;