7-24722673-G-T

Position:

• chr7-24722673-G-T

Variant summary

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

The NM_001127453.2(GSDME):​c.405-3455C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,068 control chromosomes in the GnomAD database, including 30,591 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 0.61 (30591 hom., cov: 32)
• Consequence: GSDME NM_001127453.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

GSDME (HGNC:2810): (gasdermin E) Hearing impairment is a heterogeneous condition with over 40 loci described. The protein encoded by this gene is expressed in fetal cochlea, however, its function is not known. Nonsyndromic hearing impairment is associated with a mutation in this gene. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSDME	NM_001127453.2	c.405-3455C>A		intron_variant		ENST00000645220.1	NP_001120925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSDME	ENST00000645220.1	c.405-3455C>A		intron_variant			NM_001127453.2	ENSP00000494186	P1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93181 AN: 151950 Hom.: 30521 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.614 AC: 93310 AN: 152068 Hom.: 30591 Cov.: 32 AF XY: 0.622 AC XY: 46222 AN XY: 74326

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.574

Alfa AF: 0.530 Hom.: 4529

Bravo AF: 0.628

Asia WGS AF: 0.860 AC: 2991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.045
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs2521758; hg19: chr7-24762292;