Genetic Variant GSDMD:c.410+28_410+32dupAGGGC (chr8-143559981-G-GAGGGC) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.339

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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+32dupAGGGC		intron	N/A	NP_079012.3
	GSDMD	NM_001166237.1		c.410+28_410+32dupAGGGC		intron	N/A	NP_001159709.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GSDMD	ENST00000262580.9	TSL:1 MANE Select	c.410+28_410+32dupAGGGC	intron	N/A	ENSP00000262580.4
GSDMD	ENST00000533063.5	TSL:1	c.554+28_554+32dupAGGGC	intron	N/A	ENSP00000433958.1
GSDMD	ENST00000526406.5	TSL:2	c.410+28_410+32dupAGGGC	intron	N/A	ENSP00000433209.1

Frequencies

GnomAD3 genomes

AF:

0.0931

AC:

14143

AN:

151958

Hom.:

668

Cov.:

show subpopulations

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.:

AF XY:

0.0869

AC XY:

62140

AN XY:

715088

show subpopulations

African (AFR)

AF:

0.108

AC:

3550

AN:

32782

American (AMR)

AF:

0.0493

AC:

2150

AN:

43580

Ashkenazi Jewish (ASJ)

AF:

0.0841

AC:

2162

AN:

25712

East Asian (EAS)

AF:

0.139

AC:

5494

AN:

39428

South Asian (SAS)

AF:

0.140

AC:

11874

AN:

84666

European-Finnish (FIN)

AF:

0.0882

AC:

4570

AN:

51830

Middle Eastern (MID)

AF:

0.0839

AC:

478

AN:

5698

European-Non Finnish (NFE)

AF:

0.0788

AC:

86075

AN:

1092600

Other (OTH)

AF:

0.0893

AC:

5309

AN:

59422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

5687

11375

17062

22750

28437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3244

6488

9732

12976

16220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0931

AC:

14162

AN:

152076

Hom.:

672

Cov.:

AF XY:

0.0948

AC XY:

7050

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.112

AC:

4645

AN:

41450

American (AMR)

AF:

0.0649

AC:

993

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0767

AC:

266

AN:

3470

East Asian (EAS)

AF:

0.149

AC:

772

AN:

5170

South Asian (SAS)

AF:

0.154

AC:

743

AN:

4818

European-Finnish (FIN)

AF:

0.0902

AC:

955

AN:

10590

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0810

AC:

5502

AN:

67966

Other (OTH)

AF:

0.0878

AC:

185

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

670

1340

2009

2679

3349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0586

Hom.:

183

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over