rs36001077

Positions:

• chr11-17526492-G-A
• chr11-17526492-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_153676.4(USH1C):​c.580-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,522,388 control chromosomes in the GnomAD database, including 181 homozygotes. 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 0.010 (8 hom., cov: 33)
  • Exomes 𝑓: 0.014 (173 hom.)
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0104 (1581/152278) while in subpopulation NFE AF= 0.0164 (1112/68006). AF 95% confidence interval is 0.0156. There are 8 homozygotes in gnomad4. There are 738 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1C	NM_005709.4	c.580-51C>T		intron_variant		ENST00000318024.9	NP_005700.2
USH1C	NM_153676.4	c.580-51C>T		intron_variant		ENST00000005226.12	NP_710142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.580-51C>T		intron_variant		5	NM_153676.4	ENSP00000005226
USH1C	ENST00000318024.9	c.580-51C>T		intron_variant		1	NM_005709.4	ENSP00000317018	P1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1579 AN: 152160 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.0208

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.0108 AC: 2386 AN: 220892 Hom.: 23 AF XY: 0.0108 AC XY: 1296 AN XY: 119512

Gnomad AFR exome AF: 0.00205

Gnomad AMR exome AF: 0.00464

Gnomad ASJ exome AF: 0.0113

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00372

Gnomad FIN exome AF: 0.0205

Gnomad NFE exome AF: 0.0160

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.0142 AC: 19505 AN: 1370110 Hom.: 173 Cov.: 21 AF XY: 0.0142 AC XY: 9704 AN XY: 684972

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00461

Gnomad4 ASJ exome AF: 0.0121

Gnomad4 EAS exome AF: 0.0000518

Gnomad4 SAS exome AF: 0.00391

Gnomad4 FIN exome AF: 0.0225

Gnomad4 NFE exome AF: 0.0162

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0104 AC: 1581 AN: 152278 Hom.: 8 Cov.: 33 AF XY: 0.00991 AC XY: 738 AN XY: 74464

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00310

Gnomad4 FIN AF: 0.0208

Gnomad4 NFE AF: 0.0164

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.0166 Hom.: 3

Bravo AF: 0.00833

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs36001077; hg19: chr11-17548039;