rs17253937

Positions:

• chr19-7184790-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000208.4(INSR):​c.653-153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 146,896 control chromosomes in the GnomAD database, including 1,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (1853 hom., cov: 32)
• Consequence: INSR NM_000208.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.875

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-7184790-C-T is Benign according to our data. Variant chr19-7184790-C-T is described in ClinVar as [Benign]. Clinvar id is 1246416.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSR	NM_000208.4	c.653-153G>A		intron_variant		ENST00000302850.10
INSR	NM_001079817.3	c.653-153G>A		intron_variant
INSR	XM_011527988.3	c.653-153G>A		intron_variant
INSR	XM_011527989.4	c.653-153G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSR	ENST00000302850.10	c.653-153G>A		intron_variant		1	NM_000208.4	A2
INSR	ENST00000341500.9	c.653-153G>A		intron_variant		1		P3
INSR	ENST00000598216.1	n.628-153G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 21482 AN: 146778 Hom.: 1853 Cov.: 32

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.0896

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.177

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.146 AC: 21482 AN: 146896 Hom.: 1853 Cov.: 32 AF XY: 0.151 AC XY: 10803 AN XY: 71366

Gnomad4 AFR AF: 0.0417

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.177

Alfa AF: 0.173 Hom.: 4815

Bravo AF: 0.134

Asia WGS AF: 0.167 AC: 579 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.80
CADD	Benign	8.5
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs17253937; hg19: chr19-7184801;