Variant rs35711978 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.300-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,585,054 control chromosomes in the GnomAD database, including 29,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4572 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25263 hom. )

Consequence

HEXB
NM_000521.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.373

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=-0.9).

BP6

Variant 5-74689296-C-T is Benign according to our data. Variant chr5-74689296-C-T is described in ClinVar as [Benign]. Clinvar id is 256356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.339 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.300-32C>T		intron_variant		ENST00000261416.12	NP_000512.2
HEXB	NM_001292004.2 linkuse as main transcript	c.-376-32C>T		intron_variant			NP_001278933.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
HEXB	ENST00000261416.12 linkuse as main transcript	c.300-32C>T	intron_variant	1	NM_000521.4	ENSP00000261416	P1
HEXB	ENST00000511181.5 linkuse as main transcript	c.-376-32C>T	intron_variant	1		ENSP00000426285
HEXB	ENST00000513079.5 linkuse as main transcript	n.365-32C>T	intron_variant, non_coding_transcript_variant	2
HEXB	ENST00000515528.1 linkuse as main transcript	n.355-32C>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34941

AN:

152010

Hom.:

4556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.343

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.152

Gnomad SAS

AF:

0.251

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.203

AC:

50815

AN:

250644

Hom.:

5627

AF XY:

0.200

AC XY:

27096

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.348

Gnomad AMR exome

AF:

0.253

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.182

AC:

261191

AN:

1432928

Hom.:

25263

Cov.:

AF XY:

0.183

AC XY:

131059

AN XY:

714568

show subpopulations

Gnomad4 AFR exome

AF:

0.351

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.242

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.187

GnomAD4 genome

AF:

0.230

AC:

34997

AN:

152126

Hom.:

4572

Cov.:

AF XY:

0.229

AC XY:

17043

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.344

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.196

Hom.:

603

Bravo

AF:

0.241

Asia WGS

AF:

0.230

AC:

799

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.90

CADD

Benign

3.1

DANN

Benign

0.33

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