1-156842084-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014215.3(INSRR):​c.3397+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

INSRR
NM_014215.3 intron

Scores

15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.828
Variant links:
Genes affected
INSRR (HGNC:6093): (insulin receptor related receptor) Enables transmembrane receptor protein tyrosine kinase activity. Involved in actin cytoskeleton reorganization; cellular response to alkaline pH; and protein autophosphorylation. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.054920614).
BP6
Variant 1-156842084-G-A is Benign according to our data. Variant chr1-156842084-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3064661.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
INSRRNM_014215.3 linkuse as main transcriptc.3397+28C>T intron_variant ENST00000368195.4 NP_055030.1
NTRK1NM_001007792.1 linkuse as main transcriptc.13G>A p.Ala5Thr missense_variant 2/17 NP_001007793.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
INSRRENST00000368195.4 linkuse as main transcriptc.3397+28C>T intron_variant 1 NM_014215.3 ENSP00000357178 P1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152018
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000281
AC:
7
AN:
249470
Hom.:
0
AF XY:
0.0000519
AC XY:
7
AN XY:
134770
show subpopulations
Gnomad AFR exome
AF:
0.0000622
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000132
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461116
Hom.:
0
Cov.:
33
AF XY:
0.0000206
AC XY:
15
AN XY:
726732
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000896
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000582
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152018
Hom.:
0
Cov.:
31
AF XY:
0.0000808
AC XY:
6
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000127
Hom.:
0
Bravo
AF:
0.0000756
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingCenter for Genomic Medicine, King Faisal Specialist Hospital and Research CenterMar 14, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
3.1
DANN
Benign
0.68
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.056
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.055
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PROVEAN
Benign
0.12
N
REVEL
Benign
0.081
Sift
Benign
0.95
T
Sift4G
Benign
0.88
T
Vest4
0.068
MVP
0.28
ClinPred
0.011
T
GERP RS
0.61

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.

Other links and lift over

dbSNP: rs748854792; hg19: chr1-156811876; COSMIC: COSV63872076; API