Variant 8-143559354-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_024736.7(GSDMD):c.19C>A(p.Arg7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,415,540 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

GSDMD
NM_024736.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.88

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 8-143559354-C-A is Benign according to our data. Variant chr8-143559354-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 771165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.88 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDMD	NM_024736.7 linkuse as main transcript	c.19C>A	p.Arg7=	synonymous_variant	2/11	ENST00000262580.9
GSDMD	NM_001166237.1 linkuse as main transcript	c.19C>A	p.Arg7=	synonymous_variant	5/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDMD	ENST00000262580.9 linkuse as main transcript	c.19C>A	p.Arg7=	synonymous_variant	2/11	1	NM_024736.7	P2

Frequencies

GnomAD3 genomes

AF:

0.000957

AC:

139

AN:

145200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000252

Gnomad AMI

AF:

0.00575

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00149

Gnomad OTH

AF:

0.00149

GnomAD3 exomes

AF:

0.000887

AC:

221

AN:

249206

Hom.:

AF XY:

0.000976

AC XY:

132

AN XY:

135240

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00119

AC:

1509

AN:

1270262

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

755

AN XY:

630468

show subpopulations

Gnomad4 AFR exome

AF:

0.000251

Gnomad4 AMR exome

AF:

0.00174

Gnomad4 ASJ exome

AF:

0.000106

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00139

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.000957

AC:

139

AN:

145278

Hom.:

Cov.:

AF XY:

0.000878

AC XY:

AN XY:

70626

show subpopulations

Gnomad4 AFR

AF:

0.000252

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000108

Gnomad4 NFE

AF:

0.00149

Gnomad4 OTH

AF:

0.00147

Alfa

AF:

0.000869

Hom.:

EpiCase

AF:

0.00196

EpiControl

AF:

0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	GSDMD: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.19

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over