rs1464430

Positions:

• chr15-98924705-A-C
• chr15-98924705-A-G
• chr15-98924705-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000875.5(IGF1R):​c.2782+21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,604,826 control chromosomes in the GnomAD database, including 90,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.41 (13956 hom., cov: 32)
  • Exomes 𝑓: 0.32 (76351 hom.)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-98924705-A-C is Benign according to our data. Variant chr15-98924705-A-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.2782+21A>C		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.2782+21A>C		intron_variant			NM_000875.5	P4
IGF1R	ENST00000560972.1	n.85+21A>C		intron_variant, non_coding_transcript_variant		1
IGF1R	ENST00000649865.1	c.2782+21A>C		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 60959 AN: 148624 Hom.: 13937 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.393

GnomAD3 exomes AF: 0.344 AC: 84174 AN: 244764 Hom.: 15359 AF XY: 0.333 AC XY: 44034 AN XY: 132104

Gnomad AFR exome AF: 0.664

Gnomad AMR exome AF: 0.432

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.290

Gnomad SAS exome AF: 0.283

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.309

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.317 AC: 461961 AN: 1456096 Hom.: 76351 Cov.: 31 AF XY: 0.315 AC XY: 227930 AN XY: 724720

Gnomad4 AFR exome AF: 0.646

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.336

GnomAD4 genome AF: 0.410 AC: 61014 AN: 148730 Hom.: 13956 Cov.: 32 AF XY: 0.407 AC XY: 29509 AN XY: 72586

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.388

Alfa AF: 0.309 Hom.: 1771

Bravo AF: 0.426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.024
DANN	Benign	0.70

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: rs1464430; hg19: chr15-99467934; COSMIC: COSV51296987; COSMIC: COSV51296987;