1-215844339-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_206933.4(USH2A):​c.9213G>A​(p.Ser3071Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,613,708 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S3071S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.010 ( 18 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 29 hom. )

Consequence

USH2A
NM_206933.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.152
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 1-215844339-C-T is Benign according to our data. Variant chr1-215844339-C-T is described in ClinVar as [Benign]. Clinvar id is 48616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-215844339-C-T is described in Lovd as [Benign]. Variant chr1-215844339-C-T is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.152 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1578/152266) while in subpopulation AFR AF= 0.0354 (1469/41548). AF 95% confidence interval is 0.0339. There are 18 homozygotes in gnomad4. There are 744 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USH2ANM_206933.4 linkc.9213G>A p.Ser3071Ser synonymous_variant Exon 46 of 72 ENST00000307340.8 NP_996816.3 O75445-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USH2AENST00000307340.8 linkc.9213G>A p.Ser3071Ser synonymous_variant Exon 46 of 72 1 NM_206933.4 ENSP00000305941.3 O75445-1
USH2AENST00000674083.1 linkc.9213G>A p.Ser3071Ser synonymous_variant Exon 46 of 73 ENSP00000501296.1 O75445-3

Frequencies

GnomAD3 genomes
AF:
0.0104
AC:
1576
AN:
152148
Hom.:
18
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0354
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00465
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00304
AC:
763
AN:
250628
Hom.:
8
AF XY:
0.00242
AC XY:
328
AN XY:
135440
show subpopulations
Gnomad AFR exome
AF:
0.0382
Gnomad AMR exome
AF:
0.00197
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000451
Gnomad OTH exome
AF:
0.00213
GnomAD4 exome
AF:
0.00143
AC:
2093
AN:
1461442
Hom.:
29
Cov.:
31
AF XY:
0.00131
AC XY:
950
AN XY:
727012
show subpopulations
Gnomad4 AFR exome
AF:
0.0408
Gnomad4 AMR exome
AF:
0.00255
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000325
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000361
Gnomad4 OTH exome
AF:
0.00275
GnomAD4 genome
AF:
0.0104
AC:
1578
AN:
152266
Hom.:
18
Cov.:
33
AF XY:
0.00999
AC XY:
744
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0354
Gnomad4 AMR
AF:
0.00465
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00308
Hom.:
5
Bravo
AF:
0.0121
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
May 24, 2018
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:2
Jan 12, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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. -

Jan 10, 2011
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Ser3071Ser in exon 46 of USH2A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located near a splice junction and was identified in 6/118 (5%) Black individuals (rs11103339 7). -

Usher syndrome type 2A Benign:2
Sep 16, 2020
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Nov 04, 2023
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Retinitis pigmentosa 39 Benign:1
Nov 04, 2023
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
6.2
DANN
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs111033397; hg19: chr1-216017681; API