rs4887380

chr15-88184520-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001012338.3(NTRK3):c.249-221T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,112 control chromosomes in the GnomAD database, including 4,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4382 hom., cov: 33)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.599

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 15-88184520-A-T is Benign according to our data. Variant chr15-88184520-A-T is described in ClinVar as [Benign]. Clinvar id is 1228998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.249-221T>A		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.249-221T>A		intron_variant		1	NM_001012338.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34417 AN: 151994 Hom.: 4369 Cov.: 33

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.227 AC: 34470 AN: 152112 Hom.: 4382 Cov.: 33 AF XY: 0.224 AC XY: 16660 AN XY: 74370

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.206

Alfa AF: 0.201 Hom.: 397

Bravo AF: 0.234

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.78
Dann	Benign	0.51

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: rs4887380; hg19: chr15-88727751;