11-17500539-C-T

Position:

• chr11-17500539-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_153676.4(USH1C):​c.2380+512G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,174 control chromosomes in the GnomAD database, including 5,027 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 0.21 (5027 hom., cov: 33)
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH1C	NM_005709.4	c.1480+512G>A		intron_variant		ENST00000318024.9
USH1C	NM_153676.4	c.2380+512G>A		intron_variant		ENST00000005226.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1C	ENST00000005226.12	c.2380+512G>A		intron_variant		5	NM_153676.4
USH1C	ENST00000318024.9	c.1480+512G>A		intron_variant		1	NM_005709.4	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32079 AN: 152054 Hom.: 5006 Cov.: 33

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.0866

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.211 AC: 32134 AN: 152174 Hom.: 5027 Cov.: 33 AF XY: 0.209 AC XY: 15517 AN XY: 74398

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.0504

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.0866

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.199

Alfa AF: 0.138 Hom.: 2579

Bravo AF: 0.222

Asia WGS AF: 0.194 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.9
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs878208; hg19: chr11-17522086;