rs10495013

Positions:

• chr1-215930914-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_206933.4(USH2A):​c.7300+3702A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 151,890 control chromosomes in the GnomAD database, including 137 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 0.041 (137 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

Genes affected

USH2A (HGNC:12601): (usherin) This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.7300+3702A>C		intron_variant		ENST00000307340.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.7300+3702A>C		intron_variant		1	NM_206933.4	P1
USH2A	ENST00000674083.1	c.7300+3702A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6178 AN: 151774 Hom.: 137 Cov.: 32

Gnomad AFR AF: 0.0579

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0265

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.0346

Gnomad FIN AF: 0.0410

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0450

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

GnomAD4 genome AF: 0.0407 AC: 6178 AN: 151890 Hom.: 137 Cov.: 32 AF XY: 0.0405 AC XY: 3008 AN XY: 74240

Gnomad4 AFR AF: 0.0577

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.0498

Gnomad4 SAS AF: 0.0344

Gnomad4 FIN AF: 0.0410

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0361 Hom.: 15

Bravo AF: 0.0407

Asia WGS AF: 0.0460 AC: 158 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	18
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs10495013; hg19: chr1-216104256;