Genetic Variant GSDMA:c.-5-2682G>T (chr17-39963001-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000635792.1(GSDMA):c.-5-2682G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,266 control chromosomes in the GnomAD database, including 23,721 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 23671 hom., cov: 30)

Exomes 𝑓: 0.53 ( 50 hom. )

Consequence

GSDMA
ENST00000635792.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.964

Publications

39 publications found

Variant links:

Genes affected

GSDMA (HGNC:13311): (gasdermin A) Predicted to enable phosphatidylinositol-4,5-bisphosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylserine binding activity. Involved in apoptotic process. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GSDMA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSDMA	NM_178171.5 link	c.-90G>T		upstream_gene_variant		ENST00000301659.9	NP_835465.2	Q96QA5
GSDMA	XM_017024502.3 link	c.-90G>T		upstream_gene_variant			XP_016879991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000635792.1 link	c.-5-2682G>T		intron_variant	Intron 1 of 11	5		ENSP00000490739.1		Q96QA5
GSDMA	ENST00000301659.9 link	c.-90G>T		upstream_gene_variant		1	NM_178171.5	ENSP00000301659.4		Q96QA5

Frequencies

GnomAD3 genomes

AF:

0.557

AC:

84590

AN:

151794

Hom.:

23651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.548

Gnomad AMI

AF:

0.488

Gnomad AMR

AF:

0.564

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.571

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.540

GnomAD4 exome

AF:

0.525

AC:

186

AN:

354

Hom.:

Cov.:

AF XY:

0.550

AC XY:

142

AN XY:

258

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.409

AC:

AN:

South Asian (SAS)

AF:

0.591

AC:

AN:

European-Finnish (FIN)

AF:

0.444

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.545

AC:

133

AN:

244

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.557

AC:

84645

AN:

151912

Hom.:

23671

Cov.:

AF XY:

0.556

AC XY:

41259

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.548

AC:

22683

AN:

41394

American (AMR)

AF:

0.563

AC:

8595

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1728

AN:

3468

East Asian (EAS)

AF:

0.572

AC:

2955

AN:

5168

South Asian (SAS)

AF:

0.514

AC:

2475

AN:

4814

European-Finnish (FIN)

AF:

0.548

AC:

5786

AN:

10552

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.569

AC:

38679

AN:

67934

Other (OTH)

AF:

0.541

AC:

1143

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1888

3776

5665

7553

9441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.561

Hom.:

103701

Bravo

AF:

0.564

Asia WGS

AF:

0.550

AC:

1914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

0.96

PromoterAI

0.036

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over