19-7184640-G-GGA

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.04
Variant links:
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]

Genome browser will be placed here

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
INSRNM_000208.4 linkc.653-5_653-4dupTC splice_region_variant, intron_variant Intron 2 of 21 ENST00000302850.10 NP_000199.2 P06213-1
INSRNM_001079817.3 linkc.653-5_653-4dupTC splice_region_variant, intron_variant Intron 2 of 20 NP_001073285.1 P06213-2
INSRXM_011527988.3 linkc.653-5_653-4dupTC splice_region_variant, intron_variant Intron 2 of 21 XP_011526290.2
INSRXM_011527989.4 linkc.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
INSRENST00000302850.10 linkc.653-4_653-3insTC splice_region_variant, intron_variant Intron 2 of 21 1 NM_000208.4 ENSP00000303830.4 P06213-1
INSRENST00000341500.9 linkc.653-4_653-3insTC splice_region_variant, intron_variant Intron 2 of 20 1 ENSP00000342838.4 P06213-2
INSRENST00000598216.1 linkn.628-4_628-3insTC splice_region_variant, intron_variant Intron 2 of 9 1

Frequencies

GnomAD3 genomes
AF:
0.166
AC:
23605
AN:
142072
Hom.:
3130
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.373
Gnomad AMI
AF:
0.196
Gnomad AMR
AF:
0.102
Gnomad ASJ
AF:
0.0552
Gnomad EAS
AF:
0.0803
Gnomad SAS
AF:
0.183
Gnomad FIN
AF:
0.0725
Gnomad MID
AF:
0.121
Gnomad NFE
AF:
0.0916
Gnomad OTH
AF:
0.144
GnomAD3 exomes
AF:
0.0869
AC:
11968
AN:
137742
Hom.:
157
AF XY:
0.0904
AC XY:
6935
AN XY:
76688
show subpopulations
Gnomad AFR exome
AF:
0.274
Gnomad AMR exome
AF:
0.0497
Gnomad ASJ exome
AF:
0.0507
Gnomad EAS exome
AF:
0.0640
Gnomad SAS exome
AF:
0.154
Gnomad FIN exome
AF:
0.0680
Gnomad NFE exome
AF:
0.0708
Gnomad OTH exome
AF:
0.0849
GnomAD4 exome
AF:
0.0594
AC:
73069
AN:
1230184
Hom.:
2044
Cov.:
17
AF XY:
0.0625
AC XY:
38474
AN XY:
615936
show subpopulations
Gnomad4 AFR exome
AF:
0.223
Gnomad4 AMR exome
AF:
0.0508
Gnomad4 ASJ exome
AF:
0.0428
Gnomad4 EAS exome
AF:
0.0659
Gnomad4 SAS exome
AF:
0.124
Gnomad4 FIN exome
AF:
0.0638
Gnomad4 NFE exome
AF:
0.0495
Gnomad4 OTH exome
AF:
0.0766
GnomAD4 genome
AF:
0.166
AC:
23652
AN:
142160
Hom.:
3144
Cov.:
0
AF XY:
0.165
AC XY:
11341
AN XY:
68934
show subpopulations
Gnomad4 AFR
AF:
0.374
Gnomad4 AMR
AF:
0.102
Gnomad4 ASJ
AF:
0.0552
Gnomad4 EAS
AF:
0.0799
Gnomad4 SAS
AF:
0.182
Gnomad4 FIN
AF:
0.0725
Gnomad4 NFE
AF:
0.0916
Gnomad4 OTH
AF:
0.151

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

- -

-
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

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

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

- -

Rabson-Mendenhall syndrome Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs3835070; hg19: chr19-7184651; API