NM_206933.4:c.3158-7A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The NM_206933.4(USH2A):​c.3158-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000159 in 1,613,844 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00090 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000081 ( 1 hom. )

Consequence

USH2A
NM_206933.4 splice_region, intron

Scores

2
Splicing: ADA: 0.0004707
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.108

Publications

0 publications found
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-AS1 (HGNC:40606): (USH2A antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
Variant 1-216207438-T-C is Benign according to our data. Variant chr1-216207438-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 228212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USH2ANM_206933.4 linkc.3158-7A>G splice_region_variant, intron_variant Intron 15 of 71 ENST00000307340.8 NP_996816.3 O75445-1
USH2ANM_007123.6 linkc.3158-7A>G splice_region_variant, intron_variant Intron 15 of 20 NP_009054.6 O75445-2
USH2A-AS1XR_922596.4 linkn.691+11513T>C intron_variant Intron 2 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USH2AENST00000307340.8 linkc.3158-7A>G splice_region_variant, intron_variant Intron 15 of 71 1 NM_206933.4 ENSP00000305941.3 O75445-1

Frequencies

GnomAD3 genomes
AF:
0.000881
AC:
134
AN:
152092
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00304
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
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:
0.00
Gnomad OTH
AF:
0.000957
GnomAD2 exomes
AF:
0.000191
AC:
48
AN:
250944
AF XY:
0.000118
show subpopulations
Gnomad AFR exome
AF:
0.00271
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000814
AC:
119
AN:
1461634
Hom.:
1
Cov.:
31
AF XY:
0.0000646
AC XY:
47
AN XY:
727106
show subpopulations
African (AFR)
AF:
0.00269
AC:
90
AN:
33474
American (AMR)
AF:
0.000179
AC:
8
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39624
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53410
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
0.00000270
AC:
3
AN:
1111870
Other (OTH)
AF:
0.000298
AC:
18
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.479
Heterozygous variant carriers
0
7
14
21
28
35
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000900
AC:
137
AN:
152210
Hom.:
1
Cov.:
32
AF XY:
0.000995
AC XY:
74
AN XY:
74408
show subpopulations
African (AFR)
AF:
0.00311
AC:
129
AN:
41524
American (AMR)
AF:
0.000393
AC:
6
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5168
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68012
Other (OTH)
AF:
0.000947
AC:
2
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.509
Heterozygous variant carriers
0
6
12
18
24
30
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000691
Hom.:
0
Bravo
AF:
0.000971
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Feb 26, 2015
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

c.3158-7A>G in intron 15 of USH2A: This variant is not expected to have clinical significance because it has been identified in 0.3% (28/10558) of African chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs201558076). -

Apr 29, 2025
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:2
Jan 06, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Aug 31, 2020
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Retinitis pigmentosa 39 Benign:1
Apr 11, 2023
Genome-Nilou Lab
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Usher syndrome type 2A Benign:1
Apr 11, 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
-0.38
CADD
Benign
9.5
DANN
Benign
0.84
PhyloP100
0.11
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00047
dbscSNV1_RF
Benign
0.076
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

Other links and lift over

dbSNP: rs201558076; hg19: chr1-216380780; API