chr1-156878314-A-G

Position:

• chr1-156878314-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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/exons	MANE	Protein	UniProt
NTRK1	NM_002529.4	c.1806-808A>G		intron_variant		ENST00000524377.7	NP_002520.2
NTRK1	NM_001012331.2	c.1788-808A>G		intron_variant			NP_001012331.1
NTRK1	NM_001007792.1	c.1698-808A>G		intron_variant			NP_001007793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000524377.7	c.1806-808A>G		intron_variant		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

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.796

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.904

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.804

Alfa AF: 0.864 Hom.: 55774

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2644604; hg19: chr1-156848106;