chr17-44352876-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002087.4(GRN):c.*78C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,404,270 control chromosomes in the GnomAD database, including 74,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.41 ( 14595 hom., cov: 32)
Exomes 𝑓: 0.30 ( 59842 hom. )
Consequence
GRN
NM_002087.4 3_prime_UTR
NM_002087.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.491
Genes affected
GRN (HGNC:4601): (granulin precursor) Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and PC cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively. Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 17-44352876-C-T is Benign according to our data. Variant chr17-44352876-C-T is described in ClinVar as [Benign]. Clinvar id is 29742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRN | NM_002087.4 | c.*78C>T | 3_prime_UTR_variant | 13/13 | ENST00000053867.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRN | ENST00000053867.8 | c.*78C>T | 3_prime_UTR_variant | 13/13 | 1 | NM_002087.4 | P1 | ||
GRN | ENST00000586242.1 | c.*107C>T | 3_prime_UTR_variant | 3/3 | 3 | ||||
GRN | ENST00000586443.1 | c.*224C>T | 3_prime_UTR_variant | 7/7 | 3 | ||||
GRN | ENST00000589265.5 | c.*78C>T | 3_prime_UTR_variant | 9/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.405 AC: 61476AN: 151802Hom.: 14579 Cov.: 32
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GnomAD4 exome AF: 0.300 AC: 375744AN: 1252350Hom.: 59842 Cov.: 18 AF XY: 0.300 AC XY: 188904AN XY: 629802
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ClinVar
Significance: Benign
Submissions summary: Benign:3Other:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions;C3539123:Neuronal ceroid lipofuscinosis 11 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2018 | This variant is associated with the following publications: (PMID: 25239657, 24770881, 22505994, 21212639, 29653316, 28286146, 24499389, 18723524, 20197700, 21047645, 24680777, 19016491) - |
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 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. - |
Ischemic stroke Other:1
Affects, no assertion criteria provided | case-control | Laboratory of Clinical and Experimental Pathology, Xuzhou Medical University | - | - - |
FRONTOTEMPORAL LOBAR DEGENERATION WITH UBIQUITIN-POSITIVE INCLUSIONS, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Dec 01, 2008 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at