15-98922244-C-T

Position:

chr15-98922244-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000875.5(IGF1R):c.2298C>T(p.Thr766=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 1,614,086 control chromosomes in the GnomAD database, including 5,678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 660 hom., cov: 32)

Exomes 𝑓: 0.061 ( 5018 hom. )

Consequence

IGF1R
NM_000875.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.664

Variant links:

Genes affected

IGF1R (HGNC:5465): (insulin like growth factor 1 receptor) This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

IGF1R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 15-98922244-C-T is Benign according to our data. Variant chr15-98922244-C-T is described in ClinVar as [Benign]. Clinvar id is 193818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-98922244-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.664 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5 linkuse as main transcript	c.2298C>T	p.Thr766=	synonymous_variant	11/21	ENST00000650285.1	NP_000866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
IGF1R	ENST00000650285.1 linkuse as main transcript	c.2298C>T	p.Thr766=	synonymous_variant	11/21		NM_000875.5	ENSP00000497069	P4
IGF1R	ENST00000649865.1 linkuse as main transcript	c.2298C>T	p.Thr766=	synonymous_variant	11/21			ENSP00000496919	A1
IGF1R	ENST00000561049.1 linkuse as main transcript	n.489C>T		non_coding_transcript_exon_variant	2/3	5
IGF1R	ENST00000560144.1 linkuse as main transcript			downstream_gene_variant		3		ENSP00000456950

Frequencies

GnomAD3 genomes

AF:

0.0611

AC:

9288

AN:

152112

Hom.:

659

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.349

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0431

Gnomad OTH

AF:

0.0570

GnomAD3 exomes

AF:

0.0964

AC:

24228

AN:

251438

Hom.:

2313

AF XY:

0.0935

AC XY:

12708

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.161

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.378

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.128

Gnomad NFE exome

AF:

0.0426

Gnomad OTH exome

AF:

0.0653

GnomAD4 exome

AF:

0.0614

AC:

89777

AN:

1461856

Hom.:

5018

Cov.:

AF XY:

0.0623

AC XY:

45288

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0121

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.0201

Gnomad4 EAS exome

AF:

0.330

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.0439

Gnomad4 OTH exome

AF:

0.0650

GnomAD4 genome

AF:

0.0610

AC:

9292

AN:

152230

Hom.:

660

Cov.:

AF XY:

0.0683

AC XY:

5083

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0150

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.350

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.128

Gnomad4 NFE

AF:

0.0430

Gnomad4 OTH

AF:

0.0574

Alfa

AF:

0.0450

Hom.:

392

Bravo

AF:

0.0585

Asia WGS

AF:

0.194

AC:

674

AN:

3478

EpiCase

AF:

0.0399

EpiControl

AF:

0.0388

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 06, 2018	This variant is associated with the following publications: (PMID: 20416304) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 17, 2014

- -

Growth delay due to insulin-like growth factor I resistance

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.0

DANN

Benign

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over