Variant rs41271747 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 ENST00000261416.12(HEXB):c.300-46T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 1,504,790 control chromosomes in the GnomAD database, including 7,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 505 hom., cov: 33)

Exomes 𝑓: 0.096 ( 7200 hom. )

Consequence

HEXB
ENST00000261416.12 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.258

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=-0.78).

BP6

Variant 5-74689282-T-A is Benign according to our data. Variant chr5-74689282-T-A is described in ClinVar as [Benign]. Clinvar id is 256357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEXB	NM_000521.4 linkuse as main transcript	c.300-46T>A		intron_variant		ENST00000261416.12	NP_000512.2
HEXB	NM_001292004.2 linkuse as main transcript	c.-376-46T>A		intron_variant			NP_001278933.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
HEXB	ENST00000261416.12 linkuse as main transcript	c.300-46T>A	intron_variant	1	NM_000521.4	ENSP00000261416	P1
HEXB	ENST00000511181.5 linkuse as main transcript	c.-376-46T>A	intron_variant	1		ENSP00000426285
HEXB	ENST00000513079.5 linkuse as main transcript	n.365-46T>A	intron_variant, non_coding_transcript_variant	2
HEXB	ENST00000515528.1 linkuse as main transcript	n.355-46T>A	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0702

AC:

10684

AN:

152182

Hom.:

506

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0188

Gnomad AMI

AF:

0.0892

Gnomad AMR

AF:

0.0594

Gnomad ASJ

AF:

0.0836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0240

Gnomad FIN

AF:

0.103

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0775

GnomAD3 exomes

AF:

0.0720

AC:

17981

AN:

249768

Hom.:

934

AF XY:

0.0722

AC XY:

9781

AN XY:

135416

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.0433

Gnomad ASJ exome

AF:

0.0901

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0197

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.0796

GnomAD4 exome

AF:

0.0956

AC:

129276

AN:

1352490

Hom.:

7200

Cov.:

AF XY:

0.0934

AC XY:

63457

AN XY:

679456

show subpopulations

Gnomad4 AFR exome

AF:

0.0159

Gnomad4 AMR exome

AF:

0.0461

Gnomad4 ASJ exome

AF:

0.0907

Gnomad4 EAS exome

AF:

0.0000765

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.0984

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.0890

GnomAD4 genome

AF:

0.0702

AC:

10689

AN:

152300

Hom.:

505

Cov.:

AF XY:

0.0682

AC XY:

5079

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.0595

Gnomad4 ASJ

AF:

0.0836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0246

Gnomad4 FIN

AF:

0.103

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.0767

Alfa

AF:

0.0846

Hom.:

Bravo

AF:

0.0659

Asia WGS

AF:

0.0130

AC:

AN:

3478

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	Jul 10, 2018	- -

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

-0.78

CADD

Benign

6.9

DANN

Benign

0.75

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