rs2272037

Variant names:

• chr15-98913024-T-C
• rs2272037
• NM_000875.5:c.1590-20T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-98913024-T-C
• chr15-98913024-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.26
• Publications: 26 publications found

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 Gene-Disease associations (from GenCC):

• growth delay due to insulin-like growth factor I resistance

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 284932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	c.1590-20T>C		intron_variant	Intron 7 of 20	ENST00000650285.1	NP_000866.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76419 AN: 152038 Hom.: 21244 Cov.: 33

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

GnomAD2 exomes AF: 0.584 AC: 146341 AN: 250460 AF XY: 0.588

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 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.: 26 AF XY: 0.593 AC XY: 424182 AN XY: 715682

African (AFR) AF: 0.238 AC: 7829 AN: 32938

American (AMR) AF: 0.622 AC: 27778 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 13170 AN: 25966

East Asian (EAS) AF: 0.653 AC: 25800 AN: 39530

South Asian (SAS) AF: 0.591 AC: 50625 AN: 85634

European-Finnish (FIN) AF: 0.640 AC: 34135 AN: 53344

Middle Eastern (MID) AF: 0.508 AC: 2900 AN: 5704

European-Non Finnish (NFE) AF: 0.601 AC: 653354 AN: 1087920

Other (OTH) AF: 0.567 AC: 33752 AN: 59516

GnomAD4 genome AF: 0.503 AC: 76462 AN: 152156 Hom.: 21247 Cov.: 33 AF XY: 0.509 AC XY: 37839 AN XY: 74370

African (AFR) AF: 0.250 AC: 10366 AN: 41528

American (AMR) AF: 0.569 AC: 8701 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1821 AN: 3468

East Asian (EAS) AF: 0.686 AC: 3551 AN: 5174

South Asian (SAS) AF: 0.602 AC: 2900 AN: 4814

European-Finnish (FIN) AF: 0.645 AC: 6819 AN: 10566

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40463 AN: 67994

Other (OTH) AF: 0.511 AC: 1079 AN: 2112

Alfa AF: 0.564 Hom.: 32001

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

Submissions by phenotype

not provided Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	12
DANN	Benign	0.77
PhyloP100		1.3
BranchPoint Hunter		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2272037; hg19: chr15-99456253; COSMIC: COSV51269326; COSMIC: COSV51269326;