Variant 1-156864477-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002529.4(NTRK1):c.287+49G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 1,583,284 control chromosomes in the GnomAD database, including 850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 110 hom., cov: 32)

Exomes 𝑓: 0.028 ( 740 hom. )

Consequence

NTRK1
NM_002529.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.169

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 links:

NTRK1 (HGNC:):

NTRK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-156864477-G-T is Benign according to our data. Variant chr1-156864477-G-T is described in ClinVar as [Benign]. Clinvar id is 1266752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-156864477-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NTRK1	NM_002529.4 linkuse as main transcript	c.287+49G>T	intron_variant	ENST00000524377.7	NP_002520.2	P04629-1
NTRK1	NM_001012331.2 linkuse as main transcript	c.287+49G>T	intron_variant		NP_001012331.1	P04629-2X5DR71
NTRK1	NM_001007792.1 linkuse as main transcript	c.197+49G>T	intron_variant		NP_001007793.1	P04629-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000524377.7 linkuse as main transcript	c.287+49G>T		intron_variant		1	NM_002529.4	ENSP00000431418.1		P04629-1

Frequencies

GnomAD3 genomes

AF:

0.0317

AC:

4821

AN:

152084

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0422

Gnomad AMI

AF:

0.0165

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0881

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0283

Gnomad OTH

AF:

0.0279

GnomAD3 exomes

AF:

0.0291

AC:

7162

AN:

245920

Hom.:

159

AF XY:

0.0284

AC XY:

3788

AN XY:

133194

show subpopulations

Gnomad AFR exome

AF:

0.0463

Gnomad AMR exome

AF:

0.00956

Gnomad ASJ exome

AF:

0.0171

Gnomad EAS exome

AF:

0.0941

Gnomad SAS exome

AF:

0.0251

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0254

GnomAD4 exome

AF:

0.0284

AC:

40683

AN:

1431082

Hom.:

740

Cov.:

AF XY:

0.0281

AC XY:

20050

AN XY:

713832

show subpopulations

Gnomad4 AFR exome

AF:

0.0426

Gnomad4 AMR exome

AF:

0.0106

Gnomad4 ASJ exome

AF:

0.0185

Gnomad4 EAS exome

AF:

0.0913

Gnomad4 SAS exome

AF:

0.0250

Gnomad4 FIN exome

AF:

0.0194

Gnomad4 NFE exome

AF:

0.0275

Gnomad4 OTH exome

AF:

0.0281

GnomAD4 genome

AF:

0.0317

AC:

4823

AN:

152202

Hom.:

110

Cov.:

AF XY:

0.0313

AC XY:

2332

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0422

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.0877

Gnomad4 SAS

AF:

0.0257

Gnomad4 FIN

AF:

0.0179

Gnomad4 NFE

AF:

0.0283

Gnomad4 OTH

AF:

0.0271

Alfa

AF:

0.0241

Hom.:

Bravo

AF:

0.0322

Asia WGS

AF:

0.0360

AC:

126

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.7

DANN

Benign

0.89

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over