11-17493912-C-CTGTT

Position:

• chr11-17493912-C-CTGTT

Variant summary

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

The NM_153676.4(USH1C):​c.*419_*420insAACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (69524 hom., cov: 0)
  • Exomes 𝑓: 0.96 (44235 hom.)
• Consequence: USH1C NM_153676.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.316

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]

USH1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 11-17493912-C-CTGTT is Benign according to our data. Variant chr11-17493912-C-CTGTT is described in ClinVar as [Benign]. Clinvar id is 303793.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1C	NM_153676.4	c.*419_*420insAACA		3_prime_UTR_variant	27/27	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.*451_*452insAACA		3_prime_UTR_variant	21/21	ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226	c.*419_*420insAACA		3_prime_UTR_variant	27/27	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024	c.*451_*452insAACA		3_prime_UTR_variant	21/21	1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes AF: 0.956 AC: 145261 AN: 151936 Hom.: 69480 Cov.: 0

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 0.976

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.958

GnomAD4 exome AF: 0.962 AC: 91801 AN: 95434 Hom.: 44235 Cov.: 0 AF XY: 0.959 AC XY: 46854 AN XY: 48874

Gnomad4 AFR exome AF: 0.933

Gnomad4 AMR exome AF: 0.988

Gnomad4 ASJ exome AF: 0.973

Gnomad4 EAS exome AF: 0.931

Gnomad4 SAS exome AF: 0.918

Gnomad4 FIN exome AF: 0.943

Gnomad4 NFE exome AF: 0.974

Gnomad4 OTH exome AF: 0.967

GnomAD4 genome AF: 0.956 AC: 145360 AN: 152054 Hom.: 69524 Cov.: 0 AF XY: 0.955 AC XY: 70982 AN XY: 74332

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.981

Gnomad4 ASJ AF: 0.976

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.928

Gnomad4 FIN AF: 0.937

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.953

Alfa AF: 0.948 Hom.: 2034

Asia WGS AF: 0.937 AC: 3260 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Hearing loss, autosomal recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis pigmentosa-deafness syndrome Benign:1

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: rs10626485; hg19: chr11-17515459;