rs111033277

chr11-17527210-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_153676.4(USH1C):c.496+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (0 hom., cov: 18)
  • Exomes 𝑓: 0.0017 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.303

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-17527210-T-C is Benign according to our data. Variant chr11-17527210-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 48016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH1C	NM_005709.4	c.496+13A>G		intron_variant		ENST00000318024.9
USH1C	NM_153676.4	c.496+13A>G		intron_variant		ENST00000005226.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1C	ENST00000005226.12	c.496+13A>G		intron_variant		5	NM_153676.4
USH1C	ENST00000318024.9	c.496+13A>G		intron_variant		1	NM_005709.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 566 AN: 89514 Hom.: 0 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.000669

Gnomad AMI AF: 0.0167

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00549

Gnomad EAS AF: 0.00494

Gnomad SAS AF: 0.00832

Gnomad FIN AF: 0.00630

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.00419

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00173 AC: 2042 AN: 1182250 Hom.: 0 Cov.: 30 AF XY: 0.00170 AC XY: 1004 AN XY: 591710

Gnomad4 AFR exome AF: 0.000380

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.00266

Gnomad4 EAS exome AF: 0.00664

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00302

Gnomad4 NFE exome AF: 0.00165

Gnomad4 OTH exome AF: 0.00274

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00633 AC: 567 AN: 89632 Hom.: 0 Cov.: 18 AF XY: 0.00692 AC XY: 300 AN XY: 43330

Gnomad4 AFR AF: 0.000667

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00549

Gnomad4 EAS AF: 0.00495

Gnomad4 SAS AF: 0.00874

Gnomad4 FIN AF: 0.00630

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.00413

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 27, 2011

c.496+13A>G in intron 5 of USH1C: This variant is not expected to have clinical significance because it is not located in the conserved region of the splicing c onsensus sequence. Furthermore, this variant is present in over 1% of cases. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.2
Dann	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs111033277; hg19: chr11-17548757;