NM_001007792.1:c.9+12331C>T

Variant names:

• chr1-156828169-C-T
• rs1888861
• NM_001007792.1:c.9+12331C>T

Variant summary

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

The NM_001007792.1(NTRK1):​c.9+12331C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,038 control chromosomes in the GnomAD database, including 50,582 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 (50582 hom., cov: 31)
• Consequence: NTRK1 NM_001007792.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK1	NM_001007792.1	c.9+12331C>T		intron_variant	Intron 1 of 16		NP_001007793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000392302.7	c.-64+12331C>T		intron_variant	Intron 1 of 16	5		ENSP00000376120.3
NTRK1	ENST00000674537.2	c.-203-9557C>T		intron_variant	Intron 1 of 17			ENSP00000502725.1
NTRK1	ENST00000489021.6	n.199+12331C>T		intron_variant	Intron 1 of 2	4
NTRK1	ENST00000497019.7	n.-64+12331C>T		intron_variant	Intron 1 of 15	2		ENSP00000436804.2

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123648 AN: 151920 Hom.: 50534 Cov.: 31

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.814 AC: 123750 AN: 152038 Hom.: 50582 Cov.: 31 AF XY: 0.816 AC XY: 60659 AN XY: 74312

African (AFR) AF: 0.885 AC: 36709 AN: 41472

American (AMR) AF: 0.844 AC: 12902 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2846 AN: 3470

East Asian (EAS) AF: 0.882 AC: 4559 AN: 5170

South Asian (SAS) AF: 0.763 AC: 3683 AN: 4824

European-Finnish (FIN) AF: 0.791 AC: 8337 AN: 10546

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52026 AN: 67960

Other (OTH) AF: 0.801 AC: 1688 AN: 2108

Alfa AF: 0.779 Hom.: 23426

Bravo AF: 0.826

Asia WGS AF: 0.827 AC: 2876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.1
DANN	Benign	0.21
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1888861; hg19: chr1-156797961;