Variant rs72764638 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.1082+26T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,200,260 control chromosomes in the GnomAD database, including 5,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2662 hom., cov: 30)

Exomes 𝑓: 0.11 ( 2720 hom. )

Consequence

HEXB
NM_000521.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.19

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 5-74715716-T-A is Benign according to our data. Variant chr5-74715716-T-A is described in ClinVar as [Benign]. Clinvar id is 256354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 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.1082+26T>A		intron_variant		ENST00000261416.12
HEXB	NM_001292004.2 linkuse as main transcript	c.407+26T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEXB	ENST00000261416.12 linkuse as main transcript	c.1082+26T>A		intron_variant		1	NM_000521.4	P1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

24614

AN:

141834

Hom.:

2650

Cov.:

show subpopulations

Gnomad AFR

AF:

0.302

Gnomad AMI

AF:

0.0575

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0612

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.171

GnomAD4 exome

AF:

0.113

AC:

119290

AN:

1058352

Hom.:

2720

Cov.:

AF XY:

0.112

AC XY:

60320

AN XY:

540158

show subpopulations

Gnomad4 AFR exome

AF:

0.273

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.0580

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.127

GnomAD4 genome

AF:

0.174

AC:

24662

AN:

141908

Hom.:

2662

Cov.:

AF XY:

0.173

AC XY:

11871

AN XY:

68748

show subpopulations

Gnomad4 AFR

AF:

0.302

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.178

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.0612

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.170

Alfa

AF:

0.135

Hom.:

228

Bravo

AF:

0.186

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.1

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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