rs7248104

Positions:

• chr19-7224420-G-A

Variant summary

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

The ENST00000302850.10(INSR):​c.653-39783C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,712 control chromosomes in the GnomAD database, including 11,241 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 0.38 (11241 hom., cov: 30)
• Consequence: INSR ENST00000302850.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INSR	NM_000208.4	c.653-39783C>T		intron_variant		ENST00000302850.10	NP_000199.2
INSR	NM_001079817.3	c.653-39783C>T		intron_variant			NP_001073285.1
INSR	XM_011527988.3	c.653-39783C>T		intron_variant			XP_011526290.2
INSR	XM_011527989.4	c.653-39783C>T		intron_variant			XP_011526291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INSR	ENST00000302850.10	c.653-39783C>T		intron_variant		1	NM_000208.4	ENSP00000303830	A2
INSR	ENST00000341500.9	c.653-39783C>T		intron_variant		1		ENSP00000342838	P3
INSR	ENST00000598216.1	n.628-39783C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57485 AN: 151594 Hom.: 11240 Cov.: 30

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.379 AC: 57510 AN: 151712 Hom.: 11241 Cov.: 30 AF XY: 0.382 AC XY: 28293 AN XY: 74124

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.377

Alfa AF: 0.407 Hom.: 23806

Bravo AF: 0.370

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.4
DANN	Benign	0.73

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: rs7248104; hg19: chr19-7224431;