11-17527112-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGCCCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC

Variant names:

• chr11-17527112-A-ACCTGCTCCCCCGCCCTCCCTCCCTCCCACCGTCATGGAGTACTGC
• NM_153676.4:c.496+66_497-73dupGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_153676.4(USH1C):​c.496+66_497-73dupGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 820,122 control chromosomes in the GnomAD database, including 209 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0032 (209 hom.)
  • Failed GnomAD Quality Control
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.370

Genes affected

USH1C (HGNC:12597): (USH1 protein network component harmonin) This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0032 (2628/820122) while in subpopulation AMR AF= 0.00428 (107/24984). AF 95% confidence interval is 0.00366. There are 209 homozygotes in gnomad4_exome. There are 1340 alleles in male gnomad4_exome subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 209 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4	c.496+66_497-73dupGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron_variant	Intron 5 of 26	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.496+66_497-73dupGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron_variant	Intron 5 of 20	ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron_variant	Intron 5 of 26	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9	c.497-73_497-72insGCAGTACTCCATGACGGTGGGAGGGAGGGAGGGCGGGGGAGCAGG		intron_variant	Intron 5 of 20	1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 290 AN: 66626 Hom.: 4 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00278

Gnomad AMR AF: 0.00378

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00413

Gnomad SAS AF: 0.00586

Gnomad FIN AF: 0.00307

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.00622

Gnomad OTH AF: 0.00361

GnomAD4 exome AF: 0.00320 AC: 2628 AN: 820122 Hom.: 209 Cov.: 23 AF XY: 0.00330 AC XY: 1340 AN XY: 406536

Gnomad4 AFR exome AF: 0.00164

Gnomad4 AMR exome AF: 0.00428

Gnomad4 ASJ exome AF: 0.00381

Gnomad4 EAS exome AF: 0.00428

Gnomad4 SAS exome AF: 0.00281

Gnomad4 FIN exome AF: 0.00650

Gnomad4 NFE exome AF: 0.00295

Gnomad4 OTH exome AF: 0.00443

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00433 AC: 289 AN: 66672 Hom.: 4 Cov.: 0 AF XY: 0.00393 AC XY: 121 AN XY: 30784

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00378

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00373

Gnomad4 SAS AF: 0.00585

Gnomad4 FIN AF: 0.00307

Gnomad4 NFE AF: 0.00622

Gnomad4 OTH AF: 0.00354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-17548659;