rs111033277

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_153676.4(USH1C):c.496+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 0 hom., cov: 18)

Exomes 𝑓: 0.0017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

USH1C
NM_153676.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.303

Publications

0 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-17527210-T-C is Benign according to our data. Variant chr11-17527210-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 48016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.496+13A>G		intron_variant	Intron 5 of 26	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4 link	c.496+13A>G		intron_variant	Intron 5 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.496+13A>G		intron_variant	Intron 5 of 26	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9 link	c.496+13A>G		intron_variant	Intron 5 of 20	1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes

AF:

0.00632

AC:

566

AN:

89514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000669

Gnomad AMI

AF:

0.0167

Gnomad AMR

AF:

0.0116

Gnomad ASJ

AF:

0.00549

Gnomad EAS

AF:

0.00494

Gnomad SAS

AF:

0.00832

Gnomad FIN

AF:

0.00630

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00419

GnomAD2 exomes

AF:

0.00

AC:

AN:

243214

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00173

AC:

2042

AN:

1182250

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1004

AN XY:

591710

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000380

AC:

AN:

31612

American (AMR)

AF:

0.00141

AC:

AN:

40488

Ashkenazi Jewish (ASJ)

AF:

0.00266

AC:

AN:

21426

East Asian (EAS)

AF:

0.00664

AC:

179

AN:

26958

South Asian (SAS)

AF:

0.000209

AC:

AN:

81472

European-Finnish (FIN)

AF:

0.00302

AC:

126

AN:

41728

Middle Eastern (MID)

AF:

0.000619

AC:

AN:

4848

European-Non Finnish (NFE)

AF:

0.00165

AC:

1460

AN:

885976

Other (OTH)

AF:

0.00274

AC:

131

AN:

47742

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.277

Heterozygous variant carriers

129

259

388

518

647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00633

AC:

567

AN:

89632

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

300

AN XY:

43330

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000667

AC:

AN:

34506

American (AMR)

AF:

0.0116

AC:

AN:

7666

Ashkenazi Jewish (ASJ)

AF:

0.00549

AC:

AN:

2186

East Asian (EAS)

AF:

0.00495

AC:

AN:

2426

South Asian (SAS)

AF:

0.00874

AC:

AN:

2402

European-Finnish (FIN)

AF:

0.00630

AC:

AN:

5238

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

192

European-Non Finnish (NFE)

AF:

0.0109

AC:

365

AN:

33504

Other (OTH)

AF:

0.00413

AC:

AN:

1212

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.301

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 27, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.496+13A>G in intron 5 of USH1C: This variant is not expected to have clinical significance because it is not located in the conserved region of the splicing c onsensus sequence. Furthermore, this variant is present in over 1% of cases. -

not provided

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.84

CADD

Benign

3.2

(source)

DANN

Benign

0.35

PhyloP100

-0.30

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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