19-7167940-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000208.4(INSR):​c.1610+28A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,612,784 control chromosomes in the GnomAD database, including 49,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4518 hom., cov: 31)
Exomes 𝑓: 0.25 ( 45477 hom. )

Consequence

INSR
NM_000208.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0650
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 19-7167940-T-G is Benign according to our data. Variant chr19-7167940-T-G is described in ClinVar as [Benign]. Clinvar id is 439831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
INSRNM_000208.4 linkc.1610+28A>C intron_variant ENST00000302850.10 NP_000199.2 P06213-1
INSRNM_001079817.3 linkc.1610+28A>C intron_variant NP_001073285.1 P06213-2
INSRXM_011527988.3 linkc.1610+28A>C intron_variant XP_011526290.2
INSRXM_011527989.4 linkc.1610+28A>C intron_variant XP_011526291.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
INSRENST00000302850.10 linkc.1610+28A>C intron_variant 1 NM_000208.4 ENSP00000303830.4 P06213-1
INSRENST00000341500.9 linkc.1610+28A>C intron_variant 1 ENSP00000342838.4 P06213-2
INSRENST00000598216.1 linkn.1585+28A>C intron_variant 1
INSRENST00000600492.1 linkc.11+28A>C intron_variant 5 ENSP00000473170.1 M0R3E6

Frequencies

GnomAD3 genomes
AF:
0.242
AC:
36686
AN:
151696
Hom.:
4508
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.207
Gnomad AMI
AF:
0.160
Gnomad AMR
AF:
0.244
Gnomad ASJ
AF:
0.325
Gnomad EAS
AF:
0.249
Gnomad SAS
AF:
0.266
Gnomad FIN
AF:
0.331
Gnomad MID
AF:
0.304
Gnomad NFE
AF:
0.242
Gnomad OTH
AF:
0.276
GnomAD3 exomes
AF:
0.259
AC:
64942
AN:
251092
Hom.:
8356
AF XY:
0.260
AC XY:
35306
AN XY:
135762
show subpopulations
Gnomad AFR exome
AF:
0.207
Gnomad AMR exome
AF:
0.260
Gnomad ASJ exome
AF:
0.331
Gnomad EAS exome
AF:
0.244
Gnomad SAS exome
AF:
0.257
Gnomad FIN exome
AF:
0.321
Gnomad NFE exome
AF:
0.250
Gnomad OTH exome
AF:
0.269
GnomAD4 exome
AF:
0.247
AC:
361367
AN:
1460970
Hom.:
45477
Cov.:
34
AF XY:
0.248
AC XY:
180316
AN XY:
726788
show subpopulations
Gnomad4 AFR exome
AF:
0.206
Gnomad4 AMR exome
AF:
0.258
Gnomad4 ASJ exome
AF:
0.323
Gnomad4 EAS exome
AF:
0.222
Gnomad4 SAS exome
AF:
0.263
Gnomad4 FIN exome
AF:
0.316
Gnomad4 NFE exome
AF:
0.242
Gnomad4 OTH exome
AF:
0.253
GnomAD4 genome
AF:
0.242
AC:
36730
AN:
151814
Hom.:
4518
Cov.:
31
AF XY:
0.246
AC XY:
18269
AN XY:
74132
show subpopulations
Gnomad4 AFR
AF:
0.208
Gnomad4 AMR
AF:
0.244
Gnomad4 ASJ
AF:
0.325
Gnomad4 EAS
AF:
0.249
Gnomad4 SAS
AF:
0.266
Gnomad4 FIN
AF:
0.331
Gnomad4 NFE
AF:
0.242
Gnomad4 OTH
AF:
0.277
Alfa
AF:
0.249
Hom.:
1057
Bravo
AF:
0.233
Asia WGS
AF:
0.283
AC:
984
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesSep 11, 2019- -
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
Rabson-Mendenhall syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 19, 2021- -
Leprechaunism syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 19, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.25
DANN
Benign
0.25
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs2860177; hg19: chr19-7167951; COSMIC: COSV57156805; API