1-156842014-C-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_014215.3(INSRR):c.3397+98G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000892 in 1,585,664 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0047 ( 6 hom., cov: 31)
Exomes 𝑓: 0.00049 ( 4 hom. )
Consequence
INSRR
NM_014215.3 intron
NM_014215.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.178
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 1-156842014-C-G is Benign according to our data. Variant chr1-156842014-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1215621.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0047 (715/152272) while in subpopulation AFR AF= 0.0164 (682/41562). AF 95% confidence interval is 0.0154. There are 6 homozygotes in gnomad4. There are 327 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INSRR | NM_014215.3 | c.3397+98G>C | intron_variant | ENST00000368195.4 | NP_055030.1 | |||
NTRK1 | NM_001007792.1 | c.10-67C>G | intron_variant | NP_001007793.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INSRR | ENST00000368195.4 | c.3397+98G>C | intron_variant | 1 | NM_014215.3 | ENSP00000357178 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00467 AC: 711AN: 152154Hom.: 6 Cov.: 31
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GnomAD4 exome AF: 0.000488 AC: 700AN: 1433392Hom.: 4 Cov.: 31 AF XY: 0.000405 AC XY: 288AN XY: 711404
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GnomAD4 genome AF: 0.00470 AC: 715AN: 152272Hom.: 6 Cov.: 31 AF XY: 0.00439 AC XY: 327AN XY: 74460
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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 | GeneDx | May 19, 2019 | - - |
Computational scores
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Benign
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Benign
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