rs772255621

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_014215.3(INSRR):​c.3748C>T​(p.Leu1250Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,458 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

INSRR
NM_014215.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.816
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP7
Synonymous conserved (PhyloP=0.816 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
INSRRNM_014215.3 linkc.3748C>T p.Leu1250Leu synonymous_variant Exon 22 of 22 ENST00000368195.4 NP_055030.1 P14616
NTRK1NM_001007792.1 linkc.10-1062G>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.3748C>T p.Leu1250Leu synonymous_variant Exon 22 of 22 1 NM_014215.3 ENSP00000357178.3 P14616

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455458
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
723496
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000385
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
11
DANN
Benign
0.82

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs772255621; hg19: chr1-156810811; API