ENST00000526313.5:n.*824_*825insAACA

Variant names:

• chr11-17493912-C-CTGTT
• rs10626485
• ENST00000526313.5:n.*824_*825insAACA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000526313.5(USH1C):​n.*824_*825insAACA variant causes a non coding transcript exon 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 ENST00000526313.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.316
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 1C

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
• autosomal recessive nonsyndromic hearing loss 18A

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
USH1C	NM_153676.4	c.*419_*420insAACA		3_prime_UTR_variant	Exon 27 of 27	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.*451_*452insAACA		3_prime_UTR_variant	Exon 21 of 21	ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.*419_*420insAACA		3_prime_UTR_variant	Exon 27 of 27	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9	c.*451_*452insAACA		3_prime_UTR_variant	Exon 21 of 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

African (AFR) AF: 0.933 AC: 4002 AN: 4290

American (AMR) AF: 0.988 AC: 5563 AN: 5630

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 2445 AN: 2514

East Asian (EAS) AF: 0.931 AC: 5945 AN: 6384

South Asian (SAS) AF: 0.918 AC: 10595 AN: 11538

European-Finnish (FIN) AF: 0.943 AC: 3073 AN: 3258

Middle Eastern (MID) AF: 0.983 AC: 342 AN: 348

European-Non Finnish (NFE) AF: 0.974 AC: 54919 AN: 56388

Other (OTH) AF: 0.967 AC: 4917 AN: 5084

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

African (AFR) AF: 0.932 AC: 38612 AN: 41432

American (AMR) AF: 0.981 AC: 15008 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.976 AC: 3385 AN: 3468

East Asian (EAS) AF: 0.927 AC: 4777 AN: 5152

South Asian (SAS) AF: 0.928 AC: 4474 AN: 4820

European-Finnish (FIN) AF: 0.937 AC: 9910 AN: 10576

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66129 AN: 67996

Other (OTH) AF: 0.953 AC: 2015 AN: 2114

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa-deafness syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10626485; hg19: chr11-17515459; COSMIC: COSV50013910; COSMIC: COSV50013910;