rs2240489

Variant names:

• chr11-17533367-G-A
• rs2240489
• ENST00000527720.5:c.-102C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-17533367-G-A
• chr11-17533367-G-C
• chr11-17533367-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000527720.5(USH1C):​c.-102C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000209 in 1,390,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: USH1C ENST00000527720.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 8 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 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 147786 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000514

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000392 AC: 9 AN: 229536 AF XY: 0.0000480

Gnomad AFR exome AF: 0.000136

Gnomad AMR exome AF: 0.0000299

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000386

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000217 AC: 27 AN: 1242948 Hom.: 0 Cov.: 17 AF XY: 0.0000222 AC XY: 14 AN XY: 629250

African (AFR) AF: 0.0000714 AC: 2 AN: 27992

American (AMR) AF: 0.0000456 AC: 2 AN: 43878

Ashkenazi Jewish (ASJ) AF: 0.0000404 AC: 1 AN: 24768

East Asian (EAS) AF: 0.00 AC: 0 AN: 38232

South Asian (SAS) AF: 0.0000244 AC: 2 AN: 82132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5254

European-Non Finnish (NFE) AF: 0.0000217 AC: 20 AN: 921310

Other (OTH) AF: 0.00 AC: 0 AN: 52872

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 147786 Hom.: 0 Cov.: 28 AF XY: 0.0000139 AC XY: 1 AN XY: 71822

African (AFR) AF: 0.0000514 AC: 2 AN: 38924

American (AMR) AF: 0.00 AC: 0 AN: 15066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5008

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67522

Other (OTH) AF: 0.00 AC: 0 AN: 2042

Alfa AF: 0.00 Hom.: 625

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.23
DANN	Benign	0.69
PhyloP100		-2.4
PromoterAI		0.00020	Neutral

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: rs2240489; hg19: chr11-17554914;