chr7-24698520-AT-A

Position:

• chr7-24698520-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001127453.2(GSDME):​c.*505del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 186,362 control chromosomes in the GnomAD database, including 549 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.053 (511 hom., cov: 32)
  • Exomes 𝑓: 0.016 (38 hom.)
• Consequence: GSDME NM_001127453.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.50

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 -10 ACMG points.

• BP6: Variant 7-24698520-AT-A is Benign according to our data. Variant chr7-24698520-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 359823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDME	NM_001127453.2	c.*505del		3_prime_UTR_variant	10/10	ENST00000645220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDME	ENST00000645220.1	c.*505del		3_prime_UTR_variant	10/10		NM_001127453.2	P1

Frequencies

GnomAD3 genomes AF: 0.0525 AC: 7984 AN: 151940 Hom.: 508 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0332

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00409

Gnomad OTH AF: 0.0452

GnomAD4 exome AF: 0.0159 AC: 545 AN: 34304 Hom.: 38 Cov.: 0 AF XY: 0.0157 AC XY: 271 AN XY: 17264

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0461

Gnomad4 ASJ exome AF: 0.0189

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.00643

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00283

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome AF: 0.0526 AC: 8004 AN: 152058 Hom.: 511 Cov.: 32 AF XY: 0.0535 AC XY: 3981 AN XY: 74366

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0651

Gnomad4 ASJ AF: 0.0332

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00409

Gnomad4 OTH AF: 0.0462

Alfa AF: 0.0281 Hom.: 25

Bravo AF: 0.0610

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nonsyndromic Hearing Loss, Mixed Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs77276759; hg19: chr7-24738139;