rs2860177

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

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

Conservation

PhyloP100: -0.0650

Publications

12 publications found

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]

INSR Gene-Disease associations (from GenCC):

insulin-resistance syndrome type A
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P
Donohue syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet
hyperinsulinism due to INSR deficiency
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
Rabson-Mendenhall syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)

INSR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000208.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INSR	NM_000208.4	MANE Select	c.1610+28A>C		intron	N/A	NP_000199.2	P06213-1
	INSR	NM_001079817.3		c.1610+28A>C		intron	N/A	NP_001073285.1	P06213-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INSR	ENST00000302850.10	TSL:1 MANE Select	c.1610+28A>C	intron	N/A	ENSP00000303830.4	P06213-1
INSR	ENST00000341500.9	TSL:1	c.1610+28A>C	intron	N/A	ENSP00000342838.4	P06213-2
INSR	ENST00000598216.1	TSL:1	n.1585+28A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36686

AN:

151696

Hom.:

4508

Cov.:

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

GnomAD2 exomes

AF:

0.259

AC:

64942

AN:

251092

AF XY:

0.260

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 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.:

AF XY:

0.248

AC XY:

180316

AN XY:

726788

show subpopulations

African (AFR)

AF:

0.206

AC:

6897

AN:

33454

American (AMR)

AF:

0.258

AC:

11507

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

8435

AN:

26116

East Asian (EAS)

AF:

0.222

AC:

8789

AN:

39676

South Asian (SAS)

AF:

0.263

AC:

22696

AN:

86236

European-Finnish (FIN)

AF:

0.316

AC:

16875

AN:

53360

Middle Eastern (MID)

AF:

0.305

AC:

1721

AN:

5646

European-Non Finnish (NFE)

AF:

0.242

AC:

269162

AN:

1111462

Other (OTH)

AF:

0.253

AC:

15285

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

13384

26768

40152

53536

66920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9206

18412

27618

36824

46030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.242

AC:

36730

AN:

151814

Hom.:

4518

Cov.:

AF XY:

0.246

AC XY:

18269

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.208

AC:

8605

AN:

41382

American (AMR)

AF:

0.244

AC:

3709

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.325

AC:

1126

AN:

3466

East Asian (EAS)

AF:

0.249

AC:

1285

AN:

5162

South Asian (SAS)

AF:

0.266

AC:

1275

AN:

4796

European-Finnish (FIN)

AF:

0.331

AC:

3484

AN:

10526

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16427

AN:

67948

Other (OTH)

AF:

0.277

AC:

585

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1377

2755

4132

5510

6887

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.249

Hom.:

1057

Bravo

AF:

0.233

Asia WGS

AF:

0.283

AC:

984

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Leprechaunism syndrome (1)

Rabson-Mendenhall syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.25

(source)

DANN

Benign

0.25

PhyloP100

-0.065

PromoterAI

0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over