rs2114252

Variant names:

• chr15-88121445-C-A
• rs2114252
• NM_001012338.3:c.1396+4826G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-88121445-C-A
• chr15-88121445-C-T

Variant summary

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

The NM_001012338.3(NTRK3):​c.1396+4826G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,072 control chromosomes in the GnomAD database, including 5,891 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 0.27 (5891 hom., cov: 33)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 6 publications found

Genes affected

NTRK3 (HGNC:8033): (neurotrophic receptor tyrosine kinase 3) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

NTRK3 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK3	NM_001012338.3	MANE Select	c.1396+4826G>T		intron	N/A	NP_001012338.1
	NTRK3	NM_001375810.1		c.1396+4826G>T		intron	N/A	NP_001362739.1
	NTRK3	NM_001375811.1		c.1396+4826G>T		intron	N/A	NP_001362740.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK3	ENST00000629765.3	TSL:1 MANE Select	c.1396+4826G>T		intron	N/A	ENSP00000485864.1
	NTRK3	ENST00000557856.5	TSL:1	c.1372+4826G>T		intron	N/A	ENSP00000453959.1
	NTRK3	ENST00000558676.5	TSL:1	c.1372+4826G>T		intron	N/A	ENSP00000453511.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40628 AN: 151954 Hom.: 5885 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.267 AC: 40665 AN: 152072 Hom.: 5891 Cov.: 33 AF XY: 0.260 AC XY: 19299 AN XY: 74322

African (AFR) AF: 0.349 AC: 14475 AN: 41454

American (AMR) AF: 0.264 AC: 4029 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 720 AN: 3468

East Asian (EAS) AF: 0.110 AC: 567 AN: 5172

South Asian (SAS) AF: 0.198 AC: 953 AN: 4812

European-Finnish (FIN) AF: 0.167 AC: 1766 AN: 10592

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17278 AN: 67972

Other (OTH) AF: 0.245 AC: 518 AN: 2110

Alfa AF: 0.234 Hom.: 2883

Bravo AF: 0.276

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.62
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2114252; hg19: chr15-88664676;