11-17533367-G-C

Variant names:

Variant summary

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

The ENST00000527720.5(USH1C):c.-102C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,379,248 control chromosomes in the GnomAD database, including 202,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 23430 hom., cov: 28)

Exomes 𝑓: 0.54 ( 178797 hom. )

Consequence

USH1C
ENST00000527720.5 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.38

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=-0.96).

BP6

Variant 11-17533367-G-C is Benign according to our data. Variant chr11-17533367-G-C is described in ClinVar as Benign. ClinVar VariationId is 262734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.37-45C>G		intron_variant	Intron 1 of 26	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4 link	c.37-45C>G		intron_variant	Intron 1 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.37-45C>G		intron_variant	Intron 1 of 26	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9 link	c.37-45C>G		intron_variant	Intron 1 of 20	1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

82868

AN:

146130

Hom.:

23409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.558

GnomAD2 exomes

AF:

0.540

AC:

123874

AN:

229536

AF XY:

0.541

show subpopulations

Gnomad AFR exome

AF:

0.603

Gnomad AMR exome

AF:

0.483

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.556

Gnomad FIN exome

AF:

0.585

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.535

AC:

659945

AN:

1233008

Hom.:

178797

Cov.:

AF XY:

0.537

AC XY:

335195

AN XY:

624320

show subpopulations

African (AFR)

AF:

0.636

AC:

17659

AN:

27750

American (AMR)

AF:

0.495

AC:

21534

AN:

43474

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

13697

AN:

24598

East Asian (EAS)

AF:

0.573

AC:

21668

AN:

37812

South Asian (SAS)

AF:

0.589

AC:

48245

AN:

81880

European-Finnish (FIN)

AF:

0.601

AC:

27485

AN:

45700

Middle Eastern (MID)

AF:

0.578

AC:

2992

AN:

5174

European-Non Finnish (NFE)

AF:

0.523

AC:

477754

AN:

914152

Other (OTH)

AF:

0.551

AC:

28911

AN:

52468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

12643

25286

37928

50571

63214

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12586

25172

37758

50344

62930

<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:

0.567

AC:

82928

AN:

146240

Hom.:

23430

Cov.:

AF XY:

0.569

AC XY:

40382

AN XY:

71026

show subpopulations

African (AFR)

AF:

0.632

AC:

24361

AN:

38544

American (AMR)

AF:

0.530

AC:

7888

AN:

14888

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1918

AN:

3440

East Asian (EAS)

AF:

0.566

AC:

2790

AN:

4932

South Asian (SAS)

AF:

0.587

AC:

2783

AN:

4738

European-Finnish (FIN)

AF:

0.627

AC:

5907

AN:

9418

Middle Eastern (MID)

AF:

0.577

AC:

164

AN:

284

European-Non Finnish (NFE)

AF:

0.532

AC:

35648

AN:

67056

Other (OTH)

AF:

0.558

AC:

1142

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

1595

3191

4786

6382

7977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

714

1428

2142

2856

3570

<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:

0.324

Hom.:

625

Bravo

AF:

0.581

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.96

CADD

Benign

0.15

(source)

DANN

Benign

0.34

PhyloP100

-2.4

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=300/0

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