Variant rs1665894 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000521.4(HEXB):c.558+45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 1,003,202 control chromosomes in the GnomAD database, including 413,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60329 hom., cov: 33)

Exomes 𝑓: 0.91 ( 353640 hom. )

Consequence

HEXB
NM_000521.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.08

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]

HEXB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 5-74696784-G-A is Benign according to our data. Variant chr5-74696784-G-A is described in ClinVar as [Benign]. Clinvar id is 256360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEXB	NM_000521.4 linkuse as main transcript	c.558+45G>A		intron_variant		ENST00000261416.12
HEXB	NM_001292004.2 linkuse as main transcript	c.-118+45G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
HEXB	ENST00000261416.12 linkuse as main transcript	c.558+45G>A	intron_variant	1	NM_000521.4	P1
HEXB	ENST00000511181.5 linkuse as main transcript	c.-118+45G>A	intron_variant	1
HEXB	ENST00000510820.1 linkuse as main transcript	n.277+45G>A	intron_variant, non_coding_transcript_variant	3
HEXB	ENST00000513079.5 linkuse as main transcript	n.623+45G>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.889

AC:

135267

AN:

152080

Hom.:

60279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.844

Gnomad AMI

AF:

0.948

Gnomad AMR

AF:

0.824

Gnomad ASJ

AF:

0.909

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.890

Gnomad FIN

AF:

0.948

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.924

Gnomad OTH

AF:

0.877

GnomAD3 exomes

AF:

0.890

AC:

188570

AN:

211900

Hom.:

84276

AF XY:

0.896

AC XY:

102789

AN XY:

114772

show subpopulations

Gnomad AFR exome

AF:

0.840

Gnomad AMR exome

AF:

0.774

Gnomad ASJ exome

AF:

0.910

Gnomad EAS exome

AF:

0.860

Gnomad SAS exome

AF:

0.895

Gnomad FIN exome

AF:

0.943

Gnomad NFE exome

AF:

0.927

Gnomad OTH exome

AF:

0.900

GnomAD4 exome

AF:

0.911

AC:

774943

AN:

851004

Hom.:

353640

Cov.:

AF XY:

0.911

AC XY:

406254

AN XY:

445710

show subpopulations

Gnomad4 AFR exome

AF:

0.843

Gnomad4 AMR exome

AF:

0.781

Gnomad4 ASJ exome

AF:

0.909

Gnomad4 EAS exome

AF:

0.862

Gnomad4 SAS exome

AF:

0.899

Gnomad4 FIN exome

AF:

0.944

Gnomad4 NFE exome

AF:

0.925

Gnomad4 OTH exome

AF:

0.905

GnomAD4 genome

AF:

0.889

AC:

135372

AN:

152198

Hom.:

60329

Cov.:

AF XY:

0.888

AC XY:

66111

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.844

Gnomad4 AMR

AF:

0.823

Gnomad4 ASJ

AF:

0.909

Gnomad4 EAS

AF:

0.857

Gnomad4 SAS

AF:

0.891

Gnomad4 FIN

AF:

0.948

Gnomad4 NFE

AF:

0.924

Gnomad4 OTH

AF:

0.879

Alfa

AF:

0.906

Hom.:

11591

Bravo

AF:

0.879

Asia WGS

AF:

0.851

AC:

2933

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Sandhoff disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.84

DANN

Benign

0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over