rs540751200
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 4P and 12B. PM1PM2BP4_StrongBP6_Very_Strong
The NM_002529.4(NTRK1):c.659G>A(p.Arg220Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,551,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R220W) has been classified as Likely benign.
Frequency
Consequence
NM_002529.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NTRK1 | NM_002529.4 | c.659G>A | p.Arg220Gln | missense_variant | 6/17 | ENST00000524377.7 | NP_002520.2 | |
NTRK1 | NM_001012331.2 | c.659G>A | p.Arg220Gln | missense_variant | 6/16 | NP_001012331.1 | ||
NTRK1 | NM_001007792.1 | c.569G>A | p.Arg190Gln | missense_variant | 7/17 | NP_001007793.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NTRK1 | ENST00000524377.7 | c.659G>A | p.Arg220Gln | missense_variant | 6/17 | 1 | NM_002529.4 | ENSP00000431418.1 |
Frequencies
GnomAD3 genomes AF: 0.0000985 AC: 15AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000180 AC: 28AN: 155430Hom.: 0 AF XY: 0.000219 AC XY: 18AN XY: 82108
GnomAD4 exome AF: 0.0000422 AC: 59AN: 1399588Hom.: 0 Cov.: 32 AF XY: 0.0000492 AC XY: 34AN XY: 690418
GnomAD4 genome AF: 0.0000985 AC: 15AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74490
ClinVar
Submissions by phenotype
Hereditary insensitivity to pain with anhidrosis Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 17, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2023 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | NTRK1: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at