Variant chr19-7152692-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000302850.10(INSR):c.2231+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,571,264 control chromosomes in the GnomAD database, including 7,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 882 hom., cov: 31)

Exomes 𝑓: 0.030 ( 6976 hom. )

Consequence

INSR
ENST00000302850.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.403

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 19-7152692-C-T is Benign according to our data. Variant chr19-7152692-C-T is described in ClinVar as [Benign]. Clinvar id is 1269775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
INSR	NM_000208.4 linkuse as main transcript	c.2231+34G>A	intron_variant	ENST00000302850.10	NP_000199.2
INSR	NM_001079817.3 linkuse as main transcript	c.2231+34G>A	intron_variant		NP_001073285.1
INSR	XM_011527988.3 linkuse as main transcript	c.2231+34G>A	intron_variant		XP_011526290.2
INSR	XM_011527989.4 linkuse as main transcript	c.2231+34G>A	intron_variant		XP_011526291.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSR	ENST00000302850.10 linkuse as main transcript	c.2231+34G>A	intron_variant		1	NM_000208.4	ENSP00000303830	A2	P06213-1
INSR	ENST00000341500.9 linkuse as main transcript	c.2231+34G>A	intron_variant		1		ENSP00000342838	P3	P06213-2
INSR	ENST00000598216.1 linkuse as main transcript	n.2240G>A	non_coding_transcript_exon_variant	10/10	1

Frequencies

GnomAD3 genomes

AF:

0.0428

AC:

6499

AN:

151976

Hom.:

878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.488

Gnomad SAS

AF:

0.0558

Gnomad FIN

AF:

0.0602

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00393

Gnomad OTH

AF:

0.0326

GnomAD3 exomes

AF:

0.0837

AC:

20858

AN:

249218

Hom.:

3438

AF XY:

0.0725

AC XY:

9781

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.235

Gnomad ASJ exome

AF:

0.00785

Gnomad EAS exome

AF:

0.504

Gnomad SAS exome

AF:

0.0415

Gnomad FIN exome

AF:

0.0566

Gnomad NFE exome

AF:

0.00480

Gnomad OTH exome

AF:

0.0488

GnomAD4 exome

AF:

0.0299

AC:

42399

AN:

1419170

Hom.:

6976

Cov.:

AF XY:

0.0288

AC XY:

20411

AN XY:

708250

show subpopulations

Gnomad4 AFR exome

AF:

0.00316

Gnomad4 AMR exome

AF:

0.224

Gnomad4 ASJ exome

AF:

0.00861

Gnomad4 EAS exome

AF:

0.515

Gnomad4 SAS exome

AF:

0.0405

Gnomad4 FIN exome

AF:

0.0561

Gnomad4 NFE exome

AF:

0.00264

Gnomad4 OTH exome

AF:

0.0420

GnomAD4 genome

AF:

0.0428

AC:

6509

AN:

152094

Hom.:

882

Cov.:

AF XY:

0.0509

AC XY:

3784

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00496

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.488

Gnomad4 SAS

AF:

0.0550

Gnomad4 FIN

AF:

0.0602

Gnomad4 NFE

AF:

0.00393

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.0234

Hom.:

205

Bravo

AF:

0.0521

Asia WGS

AF:

0.219

AC:

758

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.6

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over