7-24698540-A-ATACTC

Position:

• chr7-24698540-A-ATACTC

Variant summary

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

The NM_001127453.2(GSDME):​c.*485_*486insGAGTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 207,176 control chromosomes in the GnomAD database, including 218 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (153 hom., cov: 32)
  • Exomes 𝑓: 0.039 (65 hom.)
• Consequence: GSDME NM_001127453.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.248

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 7-24698540-A-ATACTC is Benign according to our data. Variant chr7-24698540-A-ATACTC is described in ClinVar as [Likely_benign]. Clinvar id is 359824.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSDME	NM_001127453.2	c.*485_*486insGAGTA		3_prime_UTR_variant	10/10	ENST00000645220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSDME	ENST00000645220.1	c.*485_*486insGAGTA		3_prime_UTR_variant	10/10		NM_001127453.2	P1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5834 AN: 152134 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.00910

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0572

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0568

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0392 AC: 2153 AN: 54924 Hom.: 65 Cov.: 0 AF XY: 0.0383 AC XY: 1065 AN XY: 27840

Gnomad4 AFR exome AF: 0.00924

Gnomad4 AMR exome AF: 0.0347

Gnomad4 ASJ exome AF: 0.0656

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0212

Gnomad4 FIN exome AF: 0.0403

Gnomad4 NFE exome AF: 0.0466

Gnomad4 OTH exome AF: 0.0367

GnomAD4 genome AF: 0.0383 AC: 5832 AN: 152252 Hom.: 153 Cov.: 32 AF XY: 0.0372 AC XY: 2773 AN XY: 74452

Gnomad4 AFR AF: 0.00907

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.0572

Gnomad4 NFE AF: 0.0568

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0462 Hom.: 17

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs201456060; hg19: chr7-24738159;