chr1-156868259-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002529.4(NTRK1):​c.574+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

NTRK1
NM_002529.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.517

Publications

0 publications found
Variant links:
Genes affected
NTRK1 (HGNC:8031): (neurotrophic receptor tyrosine kinase 1) This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, cognitive disability and cancer. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. [provided by RefSeq, Jul 2008]
NTRK1 Gene-Disease associations (from GenCC):
  • hereditary sensory and autonomic neuropathy type 4
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
  • familial medullary thyroid carcinoma
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTRK1NM_002529.4 linkc.574+10G>T intron_variant Intron 5 of 16 ENST00000524377.7 NP_002520.2 P04629-1
NTRK1NM_001012331.2 linkc.574+10G>T intron_variant Intron 5 of 15 NP_001012331.1 P04629-2X5DR71
NTRK1NM_001007792.1 linkc.484+10G>T intron_variant Intron 6 of 16 NP_001007793.1 P04629-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTRK1ENST00000524377.7 linkc.574+10G>T intron_variant Intron 5 of 16 1 NM_002529.4 ENSP00000431418.1 P04629-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1454184
Hom.:
0
Cov.:
34
AF XY:
0.00000138
AC XY:
1
AN XY:
723682
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.00
AC:
0
AN:
44702
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26126
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39688
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86216
European-Finnish (FIN)
AF:
0.0000216
AC:
1
AN:
46298
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5510
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1111864
Other (OTH)
AF:
0.00
AC:
0
AN:
60310
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
7.6
DANN
Benign
0.57
PhyloP100
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs201336491; hg19: chr1-156838051; API