rs12126638

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_206933.4(USH2A):​c.6326-1792A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,190 control chromosomes in the GnomAD database, including 2,448 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 0.17 ( 2448 hom., cov: 32)

Consequence

USH2A
NM_206933.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.370

Publications

4 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 Gene-Disease associations (from GenCC):
  • Usher syndrome type 2
    Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • Usher syndrome type 2A
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
  • retinitis pigmentosa 39
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • retinitis pigmentosa
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USH2ANM_206933.4 linkc.6326-1792A>G intron_variant Intron 32 of 71 ENST00000307340.8 NP_996816.3 O75445-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USH2AENST00000307340.8 linkc.6326-1792A>G intron_variant Intron 32 of 71 1 NM_206933.4 ENSP00000305941.3 O75445-1
USH2AENST00000674083.1 linkc.6326-1792A>G intron_variant Intron 32 of 72 ENSP00000501296.1 O75445-3

Frequencies

GnomAD3 genomes
AF:
0.174
AC:
26394
AN:
152072
Hom.:
2447
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.141
Gnomad AMI
AF:
0.160
Gnomad AMR
AF:
0.161
Gnomad ASJ
AF:
0.202
Gnomad EAS
AF:
0.0531
Gnomad SAS
AF:
0.136
Gnomad FIN
AF:
0.152
Gnomad MID
AF:
0.166
Gnomad NFE
AF:
0.210
Gnomad OTH
AF:
0.187
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.174
AC:
26407
AN:
152190
Hom.:
2448
Cov.:
32
AF XY:
0.169
AC XY:
12596
AN XY:
74416
show subpopulations
African (AFR)
AF:
0.141
AC:
5874
AN:
41548
American (AMR)
AF:
0.161
AC:
2453
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.202
AC:
702
AN:
3470
East Asian (EAS)
AF:
0.0526
AC:
272
AN:
5170
South Asian (SAS)
AF:
0.136
AC:
654
AN:
4818
European-Finnish (FIN)
AF:
0.152
AC:
1609
AN:
10612
Middle Eastern (MID)
AF:
0.154
AC:
45
AN:
292
European-Non Finnish (NFE)
AF:
0.210
AC:
14258
AN:
67982
Other (OTH)
AF:
0.187
AC:
394
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1107
2214
3322
4429
5536
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
286
572
858
1144
1430
<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:
0.190
Hom.:
5103
Bravo
AF:
0.170
Asia WGS
AF:
0.100
AC:
350
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
5.9
DANN
Benign
0.89
PhyloP100
0.37
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12126638; hg19: chr1-216175696; API