rs3753213

Positions:

• chr1-156859794-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001007792.1(NTRK1):​c.123-4560C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 152,244 control chromosomes in the GnomAD database, including 119 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 0.013 (119 hom., cov: 32)
• Consequence: NTRK1 NM_001007792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK1	NM_001007792.1	c.123-4560C>T		intron_variant			NP_001007793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000392302.7	c.51-4560C>T		intron_variant		5		ENSP00000376120.3
NTRK1	ENST00000674537.2	c.51-4560C>T		intron_variant				ENSP00000502725.1
NTRK1	ENST00000489021.6	n.313-13839C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1950 AN: 152128 Hom.: 115 Cov.: 32

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0414

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.00725

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000676

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0129 AC: 1969 AN: 152244 Hom.: 119 Cov.: 32 AF XY: 0.0140 AC XY: 1046 AN XY: 74450

Gnomad4 AFR AF: 0.00291

Gnomad4 AMR AF: 0.0895

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0413

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.00725

Gnomad4 NFE AF: 0.000676

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0103 Hom.: 15

Bravo AF: 0.0218

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.3
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3753213; hg19: chr1-156829586;