19-7184640-G-GGA
Variant names:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000208.4(INSR):c.653-5_653-4dupTC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.17 ( 3144 hom., cov: 0)
Exomes 𝑓: 0.059 ( 2044 hom. )
Consequence
INSR
NM_000208.4 splice_region, intron
NM_000208.4 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.04
Genes affected
INSR (HGNC:6091): (insulin receptor) This gene encodes a member of the receptor tyrosine kinase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form a heterotetrameric receptor. Binding of insulin or other ligands to this receptor activates the insulin signaling pathway, which regulates glucose uptake and release, as well as the synthesis and storage of carbohydrates, lipids and protein. Mutations in this gene underlie the inherited severe insulin resistance syndromes including type A insulin resistance syndrome, Donohue syndrome and Rabson-Mendenhall syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 19-7184640-G-GGA is Benign according to our data. Variant chr19-7184640-G-GGA is described in ClinVar as [Benign]. Clinvar id is 211197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INSR | NM_000208.4 | c.653-5_653-4dupTC | splice_region_variant, intron_variant | Intron 2 of 21 | ENST00000302850.10 | NP_000199.2 | ||
INSR | NM_001079817.3 | c.653-5_653-4dupTC | splice_region_variant, intron_variant | Intron 2 of 20 | NP_001073285.1 | |||
INSR | XM_011527988.3 | c.653-5_653-4dupTC | splice_region_variant, intron_variant | Intron 2 of 21 | XP_011526290.2 | |||
INSR | XM_011527989.4 | c.653-5_653-4dupTC | splice_region_variant, intron_variant | Intron 2 of 20 | XP_011526291.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INSR | ENST00000302850.10 | c.653-4_653-3insTC | splice_region_variant, intron_variant | Intron 2 of 21 | 1 | NM_000208.4 | ENSP00000303830.4 | |||
INSR | ENST00000341500.9 | c.653-4_653-3insTC | splice_region_variant, intron_variant | Intron 2 of 20 | 1 | ENSP00000342838.4 | ||||
INSR | ENST00000598216.1 | n.628-4_628-3insTC | splice_region_variant, intron_variant | Intron 2 of 9 | 1 |
Frequencies
GnomAD3 genomes AF: 0.166 AC: 23605AN: 142072Hom.: 3130 Cov.: 0
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GnomAD3 exomes AF: 0.0869 AC: 11968AN: 137742Hom.: 157 AF XY: 0.0904 AC XY: 6935AN XY: 76688
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GnomAD4 exome AF: 0.0594 AC: 73069AN: 1230184Hom.: 2044 Cov.: 17 AF XY: 0.0625 AC XY: 38474AN XY: 615936
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GnomAD4 genome AF: 0.166 AC: 23652AN: 142160Hom.: 3144 Cov.: 0 AF XY: 0.165 AC XY: 11341AN XY: 68934
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
-
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Jun 09, 2021
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
- -
not specified Benign:3
Oct 23, 2017
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Nov 18, 2014
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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Insulin-resistant diabetes mellitus AND acanthosis nigricans Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Rabson-Mendenhall syndrome Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Leprechaunism syndrome Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at