rs2041027

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.105-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,611,078 control chromosomes in the GnomAD database, including 138,990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13292 hom., cov: 32)

Exomes 𝑓: 0.41 ( 125698 hom. )

Consequence

USH1C
NM_153676.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.379

Publications

16 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=-0.82).

BP6

Variant 11-17531558-G-A is Benign according to our data. Variant chr11-17531558-G-A is described in ClinVar as Benign. ClinVar VariationId is 47972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.105-16C>T		intron_variant	Intron 2 of 26	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4 link	c.105-16C>T		intron_variant	Intron 2 of 20	ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12 link	c.105-16C>T		intron_variant	Intron 2 of 26	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9 link	c.105-16C>T		intron_variant	Intron 2 of 20	1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63368

AN:

151836

Hom.:

13285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.395

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.426

Gnomad ASJ

AF:

0.470

Gnomad EAS

AF:

0.511

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.498

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.414

Gnomad OTH

AF:

0.424

GnomAD2 exomes

AF:

0.420

AC:

104268

AN:

248282

AF XY:

0.416

show subpopulations

Gnomad AFR exome

AF:

0.394

Gnomad AMR exome

AF:

0.407

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.512

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.420

Gnomad OTH exome

AF:

0.435

GnomAD4 exome

AF:

0.413

AC:

602910

AN:

1459122

Hom.:

125698

Cov.:

AF XY:

0.411

AC XY:

298527

AN XY:

725838

show subpopulations

African (AFR)

AF:

0.396

AC:

13248

AN:

33440

American (AMR)

AF:

0.411

AC:

18373

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

12228

AN:

26124

East Asian (EAS)

AF:

0.521

AC:

20684

AN:

39684

South Asian (SAS)

AF:

0.333

AC:

28658

AN:

86082

European-Finnish (FIN)

AF:

0.487

AC:

25577

AN:

52502

Middle Eastern (MID)

AF:

0.456

AC:

2163

AN:

4742

European-Non Finnish (NFE)

AF:

0.411

AC:

457030

AN:

1111634

Other (OTH)

AF:

0.414

AC:

24949

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

21169

42337

63506

84674

105843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14048

28096

42144

56192

70240

<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:

0.417

AC:

63392

AN:

151956

Hom.:

13292

Cov.:

AF XY:

0.417

AC XY:

30965

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.394

AC:

16319

AN:

41426

American (AMR)

AF:

0.426

AC:

6504

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

1629

AN:

3464

East Asian (EAS)

AF:

0.511

AC:

2634

AN:

5150

South Asian (SAS)

AF:

0.333

AC:

1606

AN:

4816

European-Finnish (FIN)

AF:

0.498

AC:

5258

AN:

10566

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.414

AC:

28101

AN:

67946

Other (OTH)

AF:

0.422

AC:

892

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1897

3794

5691

7588

9485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<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:

0.418

Hom.:

21214

Bravo

AF:

0.416

Asia WGS

AF:

0.403

AC:

1402

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 24, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 21, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

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

- -

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

- -

Autosomal recessive nonsyndromic hearing loss 18A

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1C

Benign:1

Dec 05, 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

-0.82

CADD

Benign

2.4

(source)

DANN

Benign

0.57

PhyloP100

0.38

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over