Variant chr5-74684878-A-T 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.-376-4450A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,284 control chromosomes in the GnomAD database, including 21,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.53 ( 21513 hom., cov: 30)

Consequence

HEXB
ENST00000511181.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.451

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=-0.95).

BP6

Variant 5-74684878-A-T is Benign according to our data. Variant chr5-74684878-A-T is described in ClinVar as [Benign]. Clinvar id is 680593.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.568 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.-376-4450A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HEXB	ENST00000511181.5 linkuse as main transcript	c.-376-4450A>T		intron_variant		1

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

79869

AN:

151168

Hom.:

21500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.480

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.405

Gnomad ASJ

AF:

0.578

Gnomad EAS

AF:

0.461

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.623

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.536

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.528

AC:

79901

AN:

151284

Hom.:

21513

Cov.:

AF XY:

0.528

AC XY:

39036

AN XY:

73886

show subpopulations

Gnomad4 AFR

AF:

0.479

Gnomad4 AMR

AF:

0.404

Gnomad4 ASJ

AF:

0.578

Gnomad4 EAS

AF:

0.460

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.623

Gnomad4 NFE

AF:

0.573

Gnomad4 OTH

AF:

0.534

Alfa

AF:

0.400

Hom.:

1037

Bravo

AF:

0.507

Asia WGS

AF:

0.466

AC:

1619

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

4.9

DANN

Benign

0.46

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