rs5789990

Variant names:

• chr11-17526854-CG-C
• rs5789990
• NM_153676.4:c.522-45delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_153676.4(USH1C):​c.522-45delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7619 hom., cov: 0)
  • Exomes 𝑓: 0.32 (75262 hom.)
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.190
• Publications: 5 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 -16 ACMG points.

• BP6: Variant 11-17526854-CG-C is Benign according to our data. Variant chr11-17526854-CG-C is described in ClinVar as Benign. ClinVar VariationId is 262737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

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.522-45delC		intron	N/A	NP_710142.1	Q9Y6N9-5
	USH1C	NM_005709.4	MANE Plus Clinical	c.522-45delC		intron	N/A	NP_005700.2	A0A0S2Z4U9
	USH1C	NM_001440679.1		c.555-45delC		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.522-45delC		intron	N/A	ENSP00000005226.7	Q9Y6N9-5
	USH1C	ENST00000318024.9	TSL:1 MANE Plus Clinical	c.522-45delC		intron	N/A	ENSP00000317018.4	Q9Y6N9-1
	USH1C	ENST00000527020.5	TSL:1	c.522-45delC		intron	N/A	ENSP00000436934.1	Q9Y6N9-4

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47754 AN: 151816 Hom.: 7610 Cov.: 0

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.332

GnomAD2 exomes AF: 0.330 AC: 81327 AN: 246610 AF XY: 0.327

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.366

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.506

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.319 AC: 464102 AN: 1454582 Hom.: 75262 Cov.: 0 AF XY: 0.317 AC XY: 229760 AN XY: 723766

African (AFR) AF: 0.282 AC: 9403 AN: 33320

American (AMR) AF: 0.366 AC: 16258 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 8562 AN: 26046

East Asian (EAS) AF: 0.516 AC: 20464 AN: 39652

South Asian (SAS) AF: 0.278 AC: 23812 AN: 85688

European-Finnish (FIN) AF: 0.297 AC: 15837 AN: 53302

Middle Eastern (MID) AF: 0.329 AC: 1893 AN: 5756

European-Non Finnish (NFE) AF: 0.315 AC: 348417 AN: 1106230

Other (OTH) AF: 0.323 AC: 19456 AN: 60186

GnomAD4 genome AF: 0.314 AC: 47776 AN: 151934 Hom.: 7619 Cov.: 0 AF XY: 0.312 AC XY: 23202 AN XY: 74256

African (AFR) AF: 0.282 AC: 11689 AN: 41436

American (AMR) AF: 0.350 AC: 5349 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3470

East Asian (EAS) AF: 0.504 AC: 2573 AN: 5110

South Asian (SAS) AF: 0.277 AC: 1333 AN: 4814

European-Finnish (FIN) AF: 0.292 AC: 3089 AN: 10576

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21569 AN: 67926

Other (OTH) AF: 0.330 AC: 693 AN: 2098

Alfa AF: 0.209 Hom.: 649

Bravo AF: 0.321

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive nonsyndromic hearing loss 18A (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Usher syndrome type 1C (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.19
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs5789990; hg19: chr11-17548401;