1-156841712-G-A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014215.3(INSRR):​c.3480C>T​(p.Ala1160Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000658 in 1,614,118 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 4 hom., cov: 31)
Exomes 𝑓: 0.00039 ( 4 hom. )

Consequence

INSRR
NM_014215.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.315

Publications

1 publications found
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]
NTRK1 Gene-Disease associations (from GenCC):
  • hereditary sensory and autonomic neuropathy type 4
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
  • familial medullary thyroid carcinoma
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 1-156841712-G-A is Benign according to our data. Variant chr1-156841712-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025245.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.315 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 4 Unknown gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INSRRNM_014215.3 linkc.3480C>T p.Ala1160Ala synonymous_variant Exon 20 of 22 ENST00000368195.4 NP_055030.1 P14616
NTRK1NM_001007792.1 linkc.10-369G>A intron_variant Intron 1 of 16 NP_001007793.1 P04629-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
INSRRENST00000368195.4 linkc.3480C>T p.Ala1160Ala synonymous_variant Exon 20 of 22 1 NM_014215.3 ENSP00000357178.3 P14616

Frequencies

GnomAD3 genomes
AF:
0.00317
AC:
483
AN:
152126
Hom.:
4
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0112
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00239
GnomAD2 exomes
AF:
0.000871
AC:
219
AN:
251348
AF XY:
0.000581
show subpopulations
Gnomad AFR exome
AF:
0.0118
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.000596
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000393
AC:
575
AN:
1461874
Hom.:
4
Cov.:
33
AF XY:
0.000364
AC XY:
265
AN XY:
727248
show subpopulations
African (AFR)
AF:
0.0129
AC:
432
AN:
33480
American (AMR)
AF:
0.000335
AC:
15
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.000497
AC:
13
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000580
AC:
5
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
0.00295
AC:
17
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000261
AC:
29
AN:
1112002
Other (OTH)
AF:
0.00106
AC:
64
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
35
70
105
140
175
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00320
AC:
487
AN:
152244
Hom.:
4
Cov.:
31
AF XY:
0.00310
AC XY:
231
AN XY:
74426
show subpopulations
African (AFR)
AF:
0.0112
AC:
467
AN:
41538
American (AMR)
AF:
0.000654
AC:
10
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.000576
AC:
2
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5178
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4820
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68006
Other (OTH)
AF:
0.00237
AC:
5
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
24
47
71
94
118
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00267
Hom.:
2
Bravo
AF:
0.00373
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

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

Submissions by phenotype

not provided Benign:1
Sep 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

INSRR: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
7.3
DANN
Benign
0.86
PhyloP100
0.32
Mutation Taster
=85/15
polymorphism

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

Other links and lift over

dbSNP: rs111433413; hg19: chr1-156811504; API