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5-74684974-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000511181.5(HEXB):​c.-376-4354G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,026 control chromosomes in the GnomAD database, including 21,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 21751 hom., cov: 32)

Consequence

HEXB
ENST00000511181.5 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.276
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 5-74684974-G-C is Benign according to our data. Variant chr5-74684974-G-C is described in ClinVar as [Benign]. Clinvar id is 680596.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HEXBNM_001292004.2 linkuse as main transcriptc.-376-4354G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HEXBENST00000511181.5 linkuse as main transcriptc.-376-4354G>C intron_variant 1

Frequencies

GnomAD3 genomes
AF:
0.529
AC:
80434
AN:
151910
Hom.:
21738
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.481
Gnomad AMI
AF:
0.463
Gnomad AMR
AF:
0.406
Gnomad ASJ
AF:
0.577
Gnomad EAS
AF:
0.465
Gnomad SAS
AF:
0.552
Gnomad FIN
AF:
0.625
Gnomad MID
AF:
0.579
Gnomad NFE
AF:
0.573
Gnomad OTH
AF:
0.534
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.529
AC:
80466
AN:
152026
Hom.:
21751
Cov.:
32
AF XY:
0.530
AC XY:
39367
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.481
Gnomad4 AMR
AF:
0.405
Gnomad4 ASJ
AF:
0.577
Gnomad4 EAS
AF:
0.465
Gnomad4 SAS
AF:
0.553
Gnomad4 FIN
AF:
0.625
Gnomad4 NFE
AF:
0.573
Gnomad4 OTH
AF:
0.533
Alfa
AF:
0.410
Hom.:
1108
Bravo
AF:
0.508
Asia WGS
AF:
0.469
AC:
1631
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 19, 2018This 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
3.2
DANN
Benign
0.53

Splicing

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: rs2936918; hg19: chr5-73980799; API