rs7254060

Positions:

• chr19-7283403-A-G
• chr19-7283403-A-T

Variant summary

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

The ENST00000302850.10(INSR):​c.100+10389T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 151,936 control chromosomes in the GnomAD database, including 49,436 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 0.78 (49436 hom., cov: 30)
• Consequence: INSR ENST00000302850.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSR	NM_000208.4	c.100+10389T>C		intron_variant		ENST00000302850.10	NP_000199.2
INSR	NM_001079817.3	c.100+10389T>C		intron_variant			NP_001073285.1
INSR	XM_011527988.3	c.100+10389T>C		intron_variant			XP_011526290.2
INSR	XM_011527989.4	c.100+10389T>C		intron_variant			XP_011526291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSR	ENST00000302850.10	c.100+10389T>C		intron_variant		1	NM_000208.4	ENSP00000303830	A2
INSR	ENST00000341500.9	c.100+10389T>C		intron_variant		1		ENSP00000342838	P3
INSR	ENST00000598216.1	n.75+10389T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118501 AN: 151818 Hom.: 49431 Cov.: 30

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.780 AC: 118533 AN: 151936 Hom.: 49436 Cov.: 30 AF XY: 0.776 AC XY: 57614 AN XY: 74260

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.954

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.817

Alfa AF: 0.918 Hom.: 128567

Bravo AF: 0.762

Asia WGS AF: 0.773 AC: 2689 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.6
DANN	Benign	0.70

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: rs7254060; hg19: chr19-7283414;