rs17561000
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000521.4(HEXB):c.772-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 1,607,770 control chromosomes in the GnomAD database, including 6,249 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000521.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HEXB | NM_000521.4 | c.772-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000261416.12 | |||
HEXB | NM_001292004.2 | c.97-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HEXB | ENST00000261416.12 | c.772-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000521.4 | P1 | |||
HEXB | ENST00000511181.5 | c.97-4A>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | |||||
HEXB | ENST00000504459.5 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0672 AC: 10228AN: 152128Hom.: 430 Cov.: 32
GnomAD3 exomes AF: 0.0722 AC: 18139AN: 251386Hom.: 910 AF XY: 0.0745 AC XY: 10119AN XY: 135864
GnomAD4 exome AF: 0.0851 AC: 123929AN: 1455524Hom.: 5819 Cov.: 29 AF XY: 0.0848 AC XY: 61402AN XY: 724472
GnomAD4 genome AF: 0.0672 AC: 10230AN: 152246Hom.: 430 Cov.: 32 AF XY: 0.0676 AC XY: 5033AN XY: 74458
ClinVar
Submissions by phenotype
Sandhoff disease Benign:4
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 10, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 25, 2016 | Variant summary: The HEXB c.772-4A>G variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 8848/121370 control chromosomes (502 homozygotes) at a frequency of 0.072901, which is approximately 49 times the estimated maximal expected allele frequency of a pathogenic HEXB variant (0.001479), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 23, 2015 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 13, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at