rs10832795

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.2547-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,613,404 control chromosomes in the GnomAD database, including 136,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10581 hom., cov: 33)

Exomes 𝑓: 0.41 ( 126029 hom. )

Consequence

USH1C
NM_153676.4 intron

Scores

Splicing: ADA: 0.0006627

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.81

Publications

11 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=-0.66).

BP6

Variant 11-17495688-A-G is Benign according to our data. Variant chr11-17495688-A-G is described in ClinVar as Benign. ClinVar VariationId is 48008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.2547-11T>C		intron_variant	Intron 25 of 26	ENST00000005226.12	NP_710142.1	Q9Y6N9-5
USH1C	NM_005709.4 link	c.1646+1070T>C		intron_variant	Intron 20 of 20	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.2547-11T>C		intron_variant	Intron 25 of 26	5	NM_153676.4	ENSP00000005226.7		Q9Y6N9-5
USH1C	ENST00000318024.9 link	c.1646+1070T>C		intron_variant	Intron 20 of 20	1	NM_005709.4	ENSP00000317018.4		Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55137

AN:

152036

Hom.:

10586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.356

GnomAD2 exomes

AF:

0.410

AC:

103099

AN:

251188

AF XY:

0.412

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.508

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.412

AC:

602356

AN:

1461250

Hom.:

126029

Cov.:

AF XY:

0.413

AC XY:

300207

AN XY:

726960

show subpopulations

African (AFR)

AF:

0.225

AC:

7536

AN:

33474

American (AMR)

AF:

0.502

AC:

22443

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

9260

AN:

26132

East Asian (EAS)

AF:

0.306

AC:

12138

AN:

39692

South Asian (SAS)

AF:

0.447

AC:

38523

AN:

86240

European-Finnish (FIN)

AF:

0.419

AC:

22357

AN:

53336

Middle Eastern (MID)

AF:

0.415

AC:

2394

AN:

5762

European-Non Finnish (NFE)

AF:

0.417

AC:

463813

AN:

1111524

Other (OTH)

AF:

0.396

AC:

23892

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

19778

39557

59335

79114

98892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14186

28372

42558

56744

70930

<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:

0.362

AC:

55146

AN:

152154

Hom.:

10581

Cov.:

AF XY:

0.362

AC XY:

26916

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.235

AC:

9758

AN:

41480

American (AMR)

AF:

0.429

AC:

6554

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

1177

AN:

3470

East Asian (EAS)

AF:

0.306

AC:

1585

AN:

5184

South Asian (SAS)

AF:

0.440

AC:

2124

AN:

4822

European-Finnish (FIN)

AF:

0.407

AC:

4308

AN:

10592

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.419

AC:

28467

AN:

67998

Other (OTH)

AF:

0.351

AC:

742

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1782

3564

5346

7128

8910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.381

Hom.:

3749

Bravo

AF:

0.359

Asia WGS

AF:

0.362

AC:

1259

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 24, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Usher syndrome type 1C

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

-0.66

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00066

dbscSNV1_RF

Benign

0.074

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