rs2593641
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001292004.2(HEXB):c.-376-4450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 151,276 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 ( 0 hom., cov: 30)
Consequence
HEXB
NM_001292004.2 intron
NM_001292004.2 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.451
Publications
1 publications found
Genes affected
HEXB (HGNC:4879): (hexosaminidase subunit beta) Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]
HEXB Gene-Disease associations (from GenCC):
- Sandhoff diseaseInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen, Genomics England PanelApp, Myriad Women’s Health
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000264 AC: 4AN: 151276Hom.: 0 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
4
AN:
151276
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.0000264 AC: 4AN: 151276Hom.: 0 Cov.: 30 AF XY: 0.0000406 AC XY: 3AN XY: 73826 show subpopulations
GnomAD4 genome
AF:
AC:
4
AN:
151276
Hom.:
Cov.:
30
AF XY:
AC XY:
3
AN XY:
73826
show subpopulations
African (AFR)
AF:
AC:
3
AN:
41144
American (AMR)
AF:
AC:
0
AN:
15228
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3462
East Asian (EAS)
AF:
AC:
0
AN:
5118
South Asian (SAS)
AF:
AC:
0
AN:
4814
European-Finnish (FIN)
AF:
AC:
0
AN:
10464
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67746
Other (OTH)
AF:
AC:
0
AN:
2080
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.438
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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