rs11120620

Positions:

• chr1-215755141-T-C
• chr1-215755141-T-G

Variant summary

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

The NM_206933.4(USH2A):​c.11389+3454A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,128 control chromosomes in the GnomAD database, including 4,025 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 0.22 (4025 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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 (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH2A	NM_206933.4	c.11389+3454A>G		intron_variant		ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.11389+3454A>G		intron_variant		1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083.1	c.11389+3454A>G		intron_variant				ENSP00000501296.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33781 AN: 152008 Hom.: 4020 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.222 AC: 33811 AN: 152128 Hom.: 4025 Cov.: 32 AF XY: 0.223 AC XY: 16585 AN XY: 74358

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.221

Alfa AF: 0.184 Hom.: 3598

Bravo AF: 0.218

Asia WGS AF: 0.161 AC: 560 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	0.58
DANN	Benign	0.51

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: rs11120620; hg19: chr1-215928483;