17-39958263-A-C

Position:

• chr17-39958263-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000635792.1(GSDMA):​c.-6+4958A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,972 control chromosomes in the GnomAD database, including 32,500 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 0.65 (32500 hom., cov: 31)
• Consequence: GSDMA ENST00000635792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDMA	ENST00000635792.1	c.-6+4958A>C		intron_variant		5		ENSP00000490739	P1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98983 AN: 151854 Hom.: 32482 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.623

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.652 AC: 99048 AN: 151972 Hom.: 32500 Cov.: 31 AF XY: 0.657 AC XY: 48763 AN XY: 74270

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.624

Alfa AF: 0.638 Hom.: 13845

Bravo AF: 0.654

Asia WGS AF: 0.667 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	9.1
DANN	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7219080; hg19: chr17-38114516;