11-17498150-C-G

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.2490+12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,610,522 control chromosomes in the GnomAD database, including 10,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1183 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9640 hom. )

Consequence

USH1C
NM_153676.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.173

Publications

8 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=-0.86).

BP6

Variant 11-17498150-C-G is Benign according to our data. Variant chr11-17498150-C-G is described in ClinVar as Benign. ClinVar VariationId is 48006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153676.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
USH1C	NM_153676.4	MANE Select	c.2490+12G>C	intron	N/A	NP_710142.1
USH1C	NM_005709.4	MANE Plus Clinical	c.1590+12G>C	intron	N/A	NP_005700.2
USH1C	NM_001440679.1		c.1776+12G>C	intron	N/A	NP_001427608.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
USH1C	ENST00000005226.12	TSL:5 MANE Select	c.2490+12G>C	intron	N/A	ENSP00000005226.7
USH1C	ENST00000318024.9	TSL:1 MANE Plus Clinical	c.1590+12G>C	intron	N/A	ENSP00000317018.4
USH1C	ENST00000527020.5	TSL:1	c.1533+12G>C	intron	N/A	ENSP00000436934.1

Frequencies

GnomAD3 genomes

AF:

0.113

AC:

17161

AN:

152032

Hom.:

1178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0973

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0613

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.132

GnomAD2 exomes

AF:

0.124

AC:

31172

AN:

250950

AF XY:

0.122

show subpopulations

Gnomad AFR exome

AF:

0.0946

Gnomad AMR exome

AF:

0.158

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.313

Gnomad FIN exome

AF:

0.0632

Gnomad NFE exome

AF:

0.100

Gnomad OTH exome

AF:

0.119

GnomAD4 exome

AF:

0.106

AC:

154950

AN:

1458370

Hom.:

9640

Cov.:

AF XY:

0.107

AC XY:

77609

AN XY:

725712

show subpopulations

African (AFR)

AF:

0.0975

AC:

3259

AN:

33426

American (AMR)

AF:

0.159

AC:

7126

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

3835

AN:

26116

East Asian (EAS)

AF:

0.300

AC:

11897

AN:

39688

South Asian (SAS)

AF:

0.114

AC:

9790

AN:

86176

European-Finnish (FIN)

AF:

0.0666

AC:

3559

AN:

53402

Middle Eastern (MID)

AF:

0.187

AC:

1078

AN:

5766

European-Non Finnish (NFE)

AF:

0.0965

AC:

107003

AN:

1108804

Other (OTH)

AF:

0.123

AC:

7403

AN:

60276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

7546

15092

22638

30184

37730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4066

8132

12198

16264

20330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.113

AC:

17184

AN:

152152

Hom.:

1183

Cov.:

AF XY:

0.114

AC XY:

8501

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0975

AC:

4047

AN:

41520

American (AMR)

AF:

0.170

AC:

2590

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

543

AN:

3468

East Asian (EAS)

AF:

0.304

AC:

1568

AN:

5152

South Asian (SAS)

AF:

0.119

AC:

572

AN:

4816

European-Finnish (FIN)

AF:

0.0613

AC:

650

AN:

10598

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6804

AN:

68004

Other (OTH)

AF:

0.131

AC:

277

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

787

1574

2361

3148

3935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0731

Hom.:

112

Bravo

AF:

0.121

Asia WGS

AF:

0.204

AC:

707

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jun 24, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 03, 2015

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 13, 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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

(source)

DANN

Benign

0.58

PhyloP100

-0.17

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over