17-39954436-T-G

Variant names:

• chr17-39954436-T-G
• rs17609240
• ENST00000635792.1:c.-6+1131T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000635792.1(GSDMA):​c.-6+1131T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,078 control chromosomes in the GnomAD database, including 36,136 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 0.68 (36136 hom., cov: 32)
• Consequence: GSDMA ENST00000635792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 39 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635792.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSDMA	ENST00000635792.1	TSL:5	c.-6+1131T>G		intron	N/A	ENSP00000490739.1	Q96QA5

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104056 AN: 151960 Hom.: 36106 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.685 AC: 104139 AN: 152078 Hom.: 36136 Cov.: 32 AF XY: 0.688 AC XY: 51152 AN XY: 74322

African (AFR) AF: 0.772 AC: 32036 AN: 41486

American (AMR) AF: 0.697 AC: 10658 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2069 AN: 3466

East Asian (EAS) AF: 0.720 AC: 3712 AN: 5158

South Asian (SAS) AF: 0.689 AC: 3324 AN: 4824

European-Finnish (FIN) AF: 0.686 AC: 7248 AN: 10570

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 42994 AN: 67968

Other (OTH) AF: 0.642 AC: 1358 AN: 2114

Alfa AF: 0.648 Hom.: 83273

Bravo AF: 0.692

Asia WGS AF: 0.691 AC: 2402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.7
DANN	Benign	0.80
PhyloP100		1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17609240;

hg19: chr17-38110689;