chr19-7132070-C-T

Position:

• chr19-7132070-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000208.4(INSR):​c.2842+88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,524,078 control chromosomes in the GnomAD database, including 12,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2251 hom., cov: 31)
  • Exomes 𝑓: 0.11 (9868 hom.)
• Consequence: INSR NM_000208.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.40

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-7132070-C-T is Benign according to our data. Variant chr19-7132070-C-T is described in ClinVar as [Benign]. Clinvar id is 1282339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INSR	NM_000208.4	c.2842+88G>A		intron_variant		ENST00000302850.10
INSR	NM_001079817.3	c.2806+88G>A		intron_variant
INSR	XM_011527988.3	c.2842+88G>A		intron_variant
INSR	XM_011527989.4	c.2806+88G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INSR	ENST00000302850.10	c.2842+88G>A		intron_variant		1	NM_000208.4	A2
INSR	ENST00000341500.9	c.2806+88G>A		intron_variant		1		P3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23843 AN: 151960 Hom.: 2250 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.115 AC: 157446 AN: 1372000 Hom.: 9868 AF XY: 0.115 AC XY: 78889 AN XY: 687054

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.0629

Gnomad4 ASJ exome AF: 0.154

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.157 AC: 23864 AN: 152078 Hom.: 2251 Cov.: 31 AF XY: 0.154 AC XY: 11441 AN XY: 74320

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0852

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.154

Alfa AF: 0.0944 Hom.: 170

Bravo AF: 0.156

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.53
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

Other links and lift over

dbSNP: rs2860175; hg19: chr19-7132081;