1-156828169-C-T

Position:

• chr1-156828169-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.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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NTRK1	NM_001007792.1	c.9+12331C>T		intron_variant			NP_001007793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000392302.7	c.-64+12331C>T		intron_variant		5		ENSP00000376120
NTRK1	ENST00000674537.2	c.-203-9557C>T		intron_variant				ENSP00000502725
NTRK1	ENST00000497019.7	c.-64+12331C>T		intron_variant, NMD_transcript_variant		2		ENSP00000436804
NTRK1	ENST00000489021.6	n.199+12331C>T		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.885

Gnomad4 AMR AF: 0.844

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.882

Gnomad4 SAS AF: 0.763

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.801

Alfa AF: 0.778 Hom.: 21053

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1888861; hg19: chr1-156797961;