rs11120596

Positions:

• chr1-215677475-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206933.4(USH2A):​c.12295-1859G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 152,222 control chromosomes in the GnomAD database, including 258 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 0.052 (258 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.06 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.12295-1859G>A		intron_variant		ENST00000307340.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.12295-1859G>A		intron_variant		1	NM_206933.4	P1
USH2A	ENST00000674083.1	c.12295-1859G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0525 AC: 7982 AN: 152104 Hom.: 258 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0307

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0524 AC: 7979 AN: 152222 Hom.: 258 Cov.: 32 AF XY: 0.0539 AC XY: 4009 AN XY: 74414

Gnomad4 AFR AF: 0.0324

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.0261

Gnomad4 SAS AF: 0.0473

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0615

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0559 Hom.: 194

Bravo AF: 0.0439

Asia WGS AF: 0.0490 AC: 170 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	0.32
DANN	Benign	0.53

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: rs11120596; hg19: chr1-215850817;