chr19-7130707-A-T

Position:

• chr19-7130707-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000208.4(INSR):​c.2842+1451T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,060 control chromosomes in the GnomAD database, including 2,640 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2640 hom., cov: 31)
• Consequence: INSR NM_000208.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSR	NM_000208.4	c.2842+1451T>A		intron_variant		ENST00000302850.10	NP_000199.2
INSR	NM_001079817.3	c.2806+1451T>A		intron_variant			NP_001073285.1
INSR	XM_011527988.3	c.2842+1451T>A		intron_variant			XP_011526290.2
INSR	XM_011527989.4	c.2806+1451T>A		intron_variant			XP_011526291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSR	ENST00000302850.10	c.2842+1451T>A		intron_variant		1	NM_000208.4	ENSP00000303830.4
INSR	ENST00000341500.9	c.2806+1451T>A		intron_variant		1		ENSP00000342838.4

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27666 AN: 151940 Hom.: 2643 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.182 AC: 27681 AN: 152060 Hom.: 2640 Cov.: 31 AF XY: 0.182 AC XY: 13534 AN XY: 74338

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.190

Alfa AF: 0.177 Hom.: 325

Bravo AF: 0.178

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.51

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: rs2860174; hg19: chr19-7130718;