rs763874870
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_Very_StrongBP7BS2_Supporting
The NM_001042492.3(NF1):c.4668T>C(p.Asp1556Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,612,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001042492.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251306Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135816
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1460576Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 726572
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
Neurofibromatosis, type 1 Benign:3
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not provided Benign:2
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NF1: BP4, BP7 -
Hereditary cancer-predisposing syndrome Benign:2
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The synonymous variant NM_000267.3(NF1):c.4605T>C (p.Asp1535=) has been reported to ClinVar as Likely benign with a status of (2 stars) criteria provided, multiple submitters, no conflicts (Variation ID 413027 as of 2024-08-01). The p.Asp1535= variant is observed in 1/34,582 (0.0029%) alleles from individuals of gnomAD Latino background in gnomAD. The p.Asp1535= variant is novel (not in any individuals) in 1kG. The p.Asp1535= variant is not predicted to disrupt an existing splice site. The p.Asp1535= variant results in a substitution of a base that is not predicted conserved by GERP++ and PhyloP. For these reasons, this variant has been classified as Likely Benign. -
Neurofibromatosis, type 1;C0349639:Juvenile myelomonocytic leukemia;C0553586:Café-au-lait macules with pulmonary stenosis;C1834235:Neurofibromatosis, familial spinal;C2931482:Neurofibromatosis-Noonan syndrome Benign:1
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NF1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Hereditary cancer-predisposing syndrome;CN230736:Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: 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