dbSNP rs2272037: IGF1R:c.1590-20T>C (chr15-98913024-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000875.5(IGF1R):c.1590-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,587,368 control chromosomes in the GnomAD database, including 275,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.50 ( 21247 hom., cov: 33)

Exomes 𝑓: 0.59 ( 254272 hom. )

Consequence

IGF1R
NM_000875.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.26

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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 15-98913024-T-C is Benign according to our data. Variant chr15-98913024-T-C is described in ClinVar as [Benign]. Clinvar id is 284932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-98913024-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5 link	c.1590-20T>C		intron_variant	Intron 7 of 20	ENST00000650285.1	NP_000866.1	P08069

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF1R	ENST00000650285.1 link	c.1590-20T>C		intron_variant	Intron 7 of 20		NM_000875.5	ENSP00000497069.1		P08069

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76419

AN:

152038

Hom.:

21244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.686

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.645

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.513

GnomAD3 exomes

AF:

0.584

AC:

146341

AN:

250460

Hom.:

44006

AF XY:

0.588

AC XY:

79658

AN XY:

135468

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.624

Gnomad ASJ exome

AF:

0.514

Gnomad EAS exome

AF:

0.689

Gnomad SAS exome

AF:

0.593

Gnomad FIN exome

AF:

0.643

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.577

GnomAD4 exome

AF:

0.592

AC:

849343

AN:

1435212

Hom.:

254272

Cov.:

AF XY:

0.593

AC XY:

424182

AN XY:

715682

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.622

Gnomad4 ASJ exome

AF:

0.507

Gnomad4 EAS exome

AF:

0.653

Gnomad4 SAS exome

AF:

0.591

Gnomad4 FIN exome

AF:

0.640

Gnomad4 NFE exome

AF:

0.601

Gnomad4 OTH exome

AF:

0.567

GnomAD4 genome

AF:

0.503

AC:

76462

AN:

152156

Hom.:

21247

Cov.:

AF XY:

0.509

AC XY:

37839

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.569

Gnomad4 ASJ

AF:

0.525

Gnomad4 EAS

AF:

0.686

Gnomad4 SAS

AF:

0.602

Gnomad4 FIN

AF:

0.645

Gnomad4 NFE

AF:

0.595

Gnomad4 OTH

AF:

0.511

Alfa

AF:

0.575

Hom.:

25393

Bravo

AF:

0.483

Asia WGS

AF:

0.554

AC:

1926

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 17, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.77

BranchPoint Hunter

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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