1-215728150-C-T

Position:

chr1-215728150-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_206933.4(USH2A):c.11946G>A(p.Leu3982Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,613,994 control chromosomes in the GnomAD database, including 26,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2291 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23734 hom. )

Consequence

USH2A
NM_206933.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.729

Variant links:

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]

USH2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 1-215728150-C-T is Benign according to our data. Variant chr1-215728150-C-T is described in ClinVar as [Benign]. Clinvar id is 48387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-215728150-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.729 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH2A	NM_206933.4 linkuse as main transcript	c.11946G>A	p.Leu3982Leu	synonymous_variant	61/72	ENST00000307340.8	NP_996816.3	O75445-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8 linkuse as main transcript	c.11946G>A	p.Leu3982Leu	synonymous_variant	61/72	1	NM_206933.4	ENSP00000305941.3		O75445-1
USH2A	ENST00000674083.1 linkuse as main transcript	c.11946G>A	p.Leu3982Leu	synonymous_variant	61/73			ENSP00000501296.1		O75445-3

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25590

AN:

151994

Hom.:

2287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.00386

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.154

AC:

38659

AN:

251332

Hom.:

3508

AF XY:

0.157

AC XY:

21289

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.0795

Gnomad ASJ exome

AF:

0.192

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.176

AC:

257422

AN:

1461884

Hom.:

23734

Cov.:

AF XY:

0.176

AC XY:

128025

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.0829

Gnomad4 ASJ exome

AF:

0.190

Gnomad4 EAS exome

AF:

0.000655

Gnomad4 SAS exome

AF:

0.147

Gnomad4 FIN exome

AF:

0.224

Gnomad4 NFE exome

AF:

0.186

Gnomad4 OTH exome

AF:

0.175

GnomAD4 genome

AF:

0.168

AC:

25606

AN:

152110

Hom.:

2291

Cov.:

AF XY:

0.168

AC XY:

12467

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.00387

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.179

Hom.:

1277

Bravo

AF:

0.160

Asia WGS

AF:

0.0820

AC:

286

AN:

3478

EpiCase

AF:

0.185

EpiControl

AF:

0.187

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 04, 2014	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2011	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 19, 2008	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 22, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Usher syndrome type 2A

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

5.3

DANN

Benign

0.85

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over