rs2644604

Variant names:

• chr1-156878314-A-G
• rs2644604
• NM_002529.4:c.1806-808A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-156878314-A-G
• chr1-156878314-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002529.4(NTRK1):​c.1806-808A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,020 control chromosomes in the GnomAD database, including 50,905 homozygotes. 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: 𝑓 0.81 (50905 hom., cov: 31)
• Consequence: NTRK1 NM_002529.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK1	NM_002529.4	c.1806-808A>G		intron_variant	Intron 14 of 16	ENST00000524377.7	NP_002520.2
NTRK1	NM_001012331.2	c.1788-808A>G		intron_variant	Intron 13 of 15		NP_001012331.1
NTRK1	NM_001007792.1	c.1698-808A>G		intron_variant	Intron 14 of 16		NP_001007793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000524377.7	c.1806-808A>G		intron_variant	Intron 14 of 16	1	NM_002529.4	ENSP00000431418.1

Frequencies

GnomAD3 genomes AF: 0.810 AC: 122981 AN: 151902 Hom.: 50881 Cov.: 31

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.807

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.809 AC: 123060 AN: 152020 Hom.: 50905 Cov.: 31 AF XY: 0.803 AC XY: 59660 AN XY: 74312

African (AFR) AF: 0.726 AC: 30084 AN: 41434

American (AMR) AF: 0.796 AC: 12170 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3039 AN: 3468

East Asian (EAS) AF: 0.391 AC: 2010 AN: 5140

South Asian (SAS) AF: 0.564 AC: 2714 AN: 4810

European-Finnish (FIN) AF: 0.904 AC: 9591 AN: 10608

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.892 AC: 60628 AN: 67958

Other (OTH) AF: 0.804 AC: 1697 AN: 2110

Alfa AF: 0.859 Hom.: 72551

Bravo AF: 0.802

Asia WGS AF: 0.527 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.68
PhyloP100		0.049
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2644604; hg19: chr1-156848106;