rs9267649

Variant summary

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

The ENST00000850553.1(NEU1):​c.*2668T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,110 control chromosomes in the GnomAD database, including 58,882 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 0.88 ( 58882 hom., cov: 31)

Consequence

NEU1
ENST00000850553.1 downstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.11

Publications

38 publications found
Variant links:
Genes affected
NEU1 (HGNC:7758): (neuraminidase 1) The protein encoded by this gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis, a lysosomal storage disease that can be type 1 (cherry red spot-myoclonus syndrome or normosomatic type), which is late-onset, or type 2 (the dysmorphic type), which occurs at an earlier age with increased severity. [provided by RefSeq, Jul 2008]
NEU1 Gene-Disease associations (from GenCC):
  • sialidosis
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • sialidosis type 2
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
  • congenital sialidosis type 2
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • juvenile sialidosis type 2
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • sialidosis type 1
    Inheritance: AR 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=-1.03).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEU1ENST00000850553.1 linkc.*2668T>C downstream_gene_variant ENSP00000520846.1

Frequencies

GnomAD3 genomes
AF:
0.877
AC:
133360
AN:
151992
Hom.:
58818
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.966
Gnomad AMI
AF:
0.774
Gnomad AMR
AF:
0.914
Gnomad ASJ
AF:
0.934
Gnomad EAS
AF:
0.804
Gnomad SAS
AF:
0.882
Gnomad FIN
AF:
0.844
Gnomad MID
AF:
0.943
Gnomad NFE
AF:
0.823
Gnomad OTH
AF:
0.905
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.878
AC:
133484
AN:
152110
Hom.:
58882
Cov.:
31
AF XY:
0.878
AC XY:
65264
AN XY:
74366
show subpopulations
African (AFR)
AF:
0.966
AC:
40112
AN:
41518
American (AMR)
AF:
0.914
AC:
13959
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.934
AC:
3240
AN:
3468
East Asian (EAS)
AF:
0.804
AC:
4158
AN:
5172
South Asian (SAS)
AF:
0.882
AC:
4255
AN:
4822
European-Finnish (FIN)
AF:
0.844
AC:
8912
AN:
10562
Middle Eastern (MID)
AF:
0.942
AC:
277
AN:
294
European-Non Finnish (NFE)
AF:
0.823
AC:
55951
AN:
67976
Other (OTH)
AF:
0.905
AC:
1914
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
833
1666
2498
3331
4164
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
898
1796
2694
3592
4490
<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:
0.846
Hom.:
220521
Bravo
AF:
0.887
Asia WGS
AF:
0.895
AC:
3116
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.16
DANN
Benign
0.36
PhyloP100
-2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs9267649; hg19: chr6-31824828; API