1-156840978-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_014215.3(INSRR):c.3789G>A(p.Pro1263=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000614 in 1,613,514 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 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000065 ( 0 hom. )
Consequence
INSRR
NM_014215.3 synonymous
NM_014215.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.82
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 -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 1-156840978-C-T is Benign according to our data. Variant chr1-156840978-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1675386.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-5.82 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INSRR | NM_014215.3 | c.3789G>A | p.Pro1263= | synonymous_variant | 22/22 | ENST00000368195.4 | NP_055030.1 | |
NTRK1 | NM_001007792.1 | c.10-1103C>T | intron_variant | NP_001007793.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INSRR | ENST00000368195.4 | c.3789G>A | p.Pro1263= | synonymous_variant | 22/22 | 1 | NM_014215.3 | ENSP00000357178 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000607 AC: 15AN: 247312Hom.: 0 AF XY: 0.0000671 AC XY: 9AN XY: 134178
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GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461318Hom.: 0 Cov.: 32 AF XY: 0.0000647 AC XY: 47AN XY: 726908
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74356
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2022 | INSRR: BP4, BP7 - |
Computational scores
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Benign
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DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at