chr11-17494121-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153676.4(USH1C):c.*211A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 612,558 control chromosomes in the GnomAD database, including 61,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15358 hom., cov: 32)

Exomes 𝑓: 0.44 ( 46517 hom. )

Consequence

USH1C
NM_153676.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -6.07

Publications

17 publications found

Variant links:

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

USH1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 11-17494121-T-C is Benign according to our data. Variant chr11-17494121-T-C is described in ClinVar as [Benign]. Clinvar id is 303796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.*211A>G		3_prime_UTR_variant	Exon 27 of 27	ENST00000005226.12	NP_710142.1	Q9Y6N9-5
USH1C	NM_005709.4 link	c.*243A>G		3_prime_UTR_variant	Exon 21 of 21	ENST00000318024.9	NP_005700.2	Q9Y6N9-1A0A0S2Z4U9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12 link	c.*211A>G		3_prime_UTR_variant	Exon 27 of 27	5	NM_153676.4	ENSP00000005226.7		Q9Y6N9-5
USH1C	ENST00000318024.9 link	c.*243A>G		3_prime_UTR_variant	Exon 21 of 21	1	NM_005709.4	ENSP00000317018.4		Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67730

AN:

151572

Hom.:

15343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.447

GnomAD4 exome

AF:

0.444

AC:

204515

AN:

460864

Hom.:

46517

Cov.:

AF XY:

0.440

AC XY:

107472

AN XY:

244234

show subpopulations

African (AFR)

AF:

0.460

AC:

5792

AN:

12600

American (AMR)

AF:

0.338

AC:

7391

AN:

21882

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

6677

AN:

14072

East Asian (EAS)

AF:

0.304

AC:

9093

AN:

29882

South Asian (SAS)

AF:

0.382

AC:

18148

AN:

47552

European-Finnish (FIN)

AF:

0.466

AC:

15722

AN:

33758

Middle Eastern (MID)

AF:

0.409

AC:

793

AN:

1938

European-Non Finnish (NFE)

AF:

0.473

AC:

129530

AN:

273600

Other (OTH)

AF:

0.444

AC:

11369

AN:

25580

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5801

11601

17402

23202

29003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.447

AC:

67774

AN:

151694

Hom.:

15358

Cov.:

AF XY:

0.446

AC XY:

33044

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.454

AC:

18781

AN:

41354

American (AMR)

AF:

0.369

AC:

5621

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1681

AN:

3462

East Asian (EAS)

AF:

0.295

AC:

1518

AN:

5146

South Asian (SAS)

AF:

0.381

AC:

1831

AN:

4812

European-Finnish (FIN)

AF:

0.481

AC:

5064

AN:

10518

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.469

AC:

31844

AN:

67844

Other (OTH)

AF:

0.445

AC:

939

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1909

3818

5727

7636

9545

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.456

Hom.:

25437

Bravo

AF:

0.439

Asia WGS

AF:

0.357

AC:

1241

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1C

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal recessive nonsyndromic hearing loss 18A

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.032

(source)

DANN

Benign

0.51

PhyloP100

-6.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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chr11-17494121-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over