15-98924602-C-T

Position:

chr15-98924602-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000875.5(IGF1R):c.2700C>T(p.Asn900Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 1,614,036 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 19 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 71 hom. )

Consequence

IGF1R
NM_000875.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.15

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:

IGF1R (HGNC:):

IGF1R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 15-98924602-C-T is Benign according to our data. Variant chr15-98924602-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 194185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-98924602-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.15 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00715 (1089/152306) while in subpopulation NFE AF= 0.00779 (530/68028). AF 95% confidence interval is 0.00724. There are 19 homozygotes in gnomad4. There are 625 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF1R	NM_000875.5 linkuse as main transcript	c.2700C>T	p.Asn900Asn	synonymous_variant	13/21	ENST00000650285.1	NP_000866.1	P08069

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGF1R	ENST00000650285.1 linkuse as main transcript	c.2700C>T	p.Asn900Asn	synonymous_variant	13/21		NM_000875.5	ENSP00000497069.1	P08069
IGF1R	ENST00000560972.1 linkuse as main transcript	n.3C>T		non_coding_transcript_exon_variant	1/4	1
IGF1R	ENST00000649865.1 linkuse as main transcript	c.2700C>T	p.Asn900Asn	synonymous_variant	13/21			ENSP00000496919.1	C9J5X1
IGF1R	ENST00000560343.1 linkuse as main transcript	n.309C>T		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.00716

AC:

1090

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0425

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00779

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00721

AC:

1814

AN:

251494

Hom.:

AF XY:

0.00727

AC XY:

988

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.0375

Gnomad NFE exome

AF:

0.00708

Gnomad OTH exome

AF:

0.00717

GnomAD4 exome

AF:

0.00656

AC:

9590

AN:

1461730

Hom.:

Cov.:

AF XY:

0.00650

AC XY:

4727

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00474

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.00635

Gnomad4 OTH exome

AF:

0.00628

GnomAD4 genome

AF:

0.00715

AC:

1089

AN:

152306

Hom.:

Cov.:

AF XY:

0.00839

AC XY:

625

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0425

Gnomad4 NFE

AF:

0.00779

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00595

Hom.:

Bravo

AF:

0.00366

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00665

EpiControl

AF:

0.00587

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	IGF1R: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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)

May 26, 2015

- -

Growth delay due to insulin-like growth factor I resistance

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.89

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