rs2272037

chr15-98913024-T-Cchr15-98913024-T-G

Variant summary

Our verdict is Benign. Variant got -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 (★★).

• 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:2
• Conservation: PhyloP100: 1.26

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: 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/exons	MANE	UniProt
IGF1R	NM_000875.5	c.1590-20T>C		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.1590-20T>C		intron_variant			NM_000875.5	P4
IGF1R	ENST00000559925.5	n.1590-20T>C		intron_variant, non_coding_transcript_variant		1
IGF1R	ENST00000649865.1	c.1590-20T>C		intron_variant				A1
IGF1R	ENST00000559582.1	n.497-20T>C		intron_variant, non_coding_transcript_variant		4

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

GnomAD3 exomes AF: 0.584 AC: 146341 AN: 250460 Hom.: 44006 AF XY: 0.588 AC XY: 79658 AN XY: 135468

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

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.: 33 AF XY: 0.509 AC XY: 37839 AN XY: 74370

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 17, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	12
Dann	Benign	0.77
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

Other links and lift over

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