chr17-31325820-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_001042492.3(NF1):c.4836G>A(p.Arg1612=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. R1612R) has been classified as Likely benign.
Frequency
Consequence
NM_001042492.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NF1 | NM_001042492.3 | c.4836G>A | p.Arg1612= | splice_region_variant, synonymous_variant | 37/58 | ENST00000358273.9 | |
NF1 | NM_000267.3 | c.4773G>A | p.Arg1591= | splice_region_variant, synonymous_variant | 36/57 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NF1 | ENST00000358273.9 | c.4836G>A | p.Arg1612= | splice_region_variant, synonymous_variant | 37/58 | 1 | NM_001042492.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151960Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461234Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726982
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151960Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74224
ClinVar
Submissions by phenotype
Craniopharyngioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Mar 02, 2017 | - - |
Neurofibromatosis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 23, 2023 | - - |
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at