rs72824736
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002087.4(GRN):c.835+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 1,614,032 control chromosomes in the GnomAD database, including 4,152 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_002087.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRN | NM_002087.4 | c.835+7G>A | splice_region_variant, intron_variant | ENST00000053867.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRN | ENST00000053867.8 | c.835+7G>A | splice_region_variant, intron_variant | 1 | NM_002087.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0461 AC: 7013AN: 152210Hom.: 250 Cov.: 33
GnomAD3 exomes AF: 0.0455 AC: 11432AN: 251256Hom.: 400 AF XY: 0.0451 AC XY: 6124AN XY: 135804
GnomAD4 exome AF: 0.0668 AC: 97640AN: 1461704Hom.: 3902 Cov.: 34 AF XY: 0.0645 AC XY: 46916AN XY: 727164
GnomAD4 genome ? AF: 0.0460 AC: 7008AN: 152328Hom.: 250 Cov.: 33 AF XY: 0.0435 AC XY: 3237AN XY: 74488
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
not provided Benign:2
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 22, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 17, 2018 | - - |
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 20, 2017 | - - |
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. - |
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions;C3539123:Neuronal ceroid lipofuscinosis 11 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at