Variant chr5-74685086-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000511181.5(HEXB):c.-376-4242G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 657,114 control chromosomes in the GnomAD database, including 421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 330 hom., cov: 33)

Exomes 𝑓: 0.0036 ( 91 hom. )

Consequence

HEXB
ENST00000511181.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.03

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 5-74685086-G-A is Benign according to our data. Variant chr5-74685086-G-A is described in ClinVar as [Benign]. Clinvar id is 1275326.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HEXB	NM_001292004.2 linkuse as main transcript	c.-376-4242G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEXB	ENST00000511181.5 linkuse as main transcript	c.-376-4242G>A		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5481

AN:

151822

Hom.:

327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000383

Gnomad OTH

AF:

0.0217

GnomAD4 exome

AF:

0.00359

AC:

1816

AN:

505174

Hom.:

AF XY:

0.00308

AC XY:

809

AN XY:

262720

show subpopulations

Gnomad4 AFR exome

AF:

0.125

Gnomad4 AMR exome

AF:

0.00914

Gnomad4 ASJ exome

AF:

0.00788

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000461

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.00928

GnomAD4 genome

AF:

0.0362

AC:

5500

AN:

151940

Hom.:

330

Cov.:

AF XY:

0.0358

AC XY:

2656

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.0117

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000383

Gnomad4 OTH

AF:

0.0214

Alfa

AF:

0.0282

Hom.:

Bravo

AF:

0.0409

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Sandhoff disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.9

DANN

Benign

0.66

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.

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