rs111033277

Variant names:

• chr11-17527210-T-C
• rs111033277
• NM_153676.4:c.496+13A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-17527210-T-C
• chr11-17527210-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.303
• Publications: 0 publications found

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 1C

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, G2P
• Usher syndrome type 1

  Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• autosomal recessive nonsyndromic hearing loss 18A

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH1C	NM_153676.4	MANE Select	c.496+13A>G		intron	N/A	NP_710142.1	Q9Y6N9-5
	USH1C	NM_005709.4	MANE Plus Clinical	c.496+13A>G		intron	N/A	NP_005700.2	A0A0S2Z4U9
	USH1C	NM_001440679.1		c.529+13A>G		intron	N/A	NP_001427608.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH1C	ENST00000005226.12	TSL:5 MANE Select	c.496+13A>G		intron	N/A	ENSP00000005226.7	Q9Y6N9-5
	USH1C	ENST00000318024.9	TSL:1 MANE Plus Clinical	c.496+13A>G		intron	N/A	ENSP00000317018.4	Q9Y6N9-1
	USH1C	ENST00000527020.5	TSL:1	c.496+13A>G		intron	N/A	ENSP00000436934.1	Q9Y6N9-4

Frequencies

GnomAD3 genomes AF: 0.00632 AC: 566 AN: 89514 Hom.: 0 Cov.: 18

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: 0 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.: 0 Cov.: 30 AF XY: 0.00170 AC XY: 1004 AN XY: 591710

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

African (AFR) AF: 0.000380 AC: 12 AN: 31612

American (AMR) AF: 0.00141 AC: 57 AN: 40488

Ashkenazi Jewish (ASJ) AF: 0.00266 AC: 57 AN: 21426

East Asian (EAS) AF: 0.00664 AC: 179 AN: 26958

South Asian (SAS) AF: 0.000209 AC: 17 AN: 81472

European-Finnish (FIN) AF: 0.00302 AC: 126 AN: 41728

Middle Eastern (MID) AF: 0.000619 AC: 3 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00633 AC: 567 AN: 89632 Hom.: 0 Cov.: 18 AF XY: 0.00692 AC XY: 300 AN XY: 43330

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

African (AFR) AF: 0.000667 AC: 23 AN: 34506

American (AMR) AF: 0.0116 AC: 89 AN: 7666

Ashkenazi Jewish (ASJ) AF: 0.00549 AC: 12 AN: 2186

East Asian (EAS) AF: 0.00495 AC: 12 AN: 2426

South Asian (SAS) AF: 0.00874 AC: 21 AN: 2402

European-Finnish (FIN) AF: 0.00630 AC: 33 AN: 5238

Middle Eastern (MID) AF: 0.0104 AC: 2 AN: 192

European-Non Finnish (NFE) AF: 0.0109 AC: 365 AN: 33504

Other (OTH) AF: 0.00413 AC: 5 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.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.35
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs111033277; hg19: chr11-17548757;