rs2593053

Positions:

• chr15-98957027-G-A
• chr15-98957027-G-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.3723-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,612,068 control chromosomes in the GnomAD database, including 122,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.32 (8442 hom., cov: 33)
  • Exomes 𝑓: 0.39 (114256 hom.)
• Consequence: IGF1R NM_000875.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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]

SYNM-AS1 (HGNC:55421): (SYNM antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-98957027-G-A is Benign according to our data. Variant chr15-98957027-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.3723-34G>A		intron_variant		ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.3723-34G>A		intron_variant			NM_000875.5	P4
SYNM-AS1	ENST00000559468.1	n.349-2639C>T		intron_variant, non_coding_transcript_variant		4
IGF1R	ENST00000649865.1	c.3720-34G>A		intron_variant				A1
IGF1R	ENST00000558751.1	n.317-34G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48009 AN: 151968 Hom.: 8444 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.344

GnomAD3 exomes AF: 0.353 AC: 88485 AN: 250576 Hom.: 16521 AF XY: 0.364 AC XY: 49259 AN XY: 135476

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.253

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.271

Gnomad SAS exome AF: 0.398

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.406

Gnomad OTH exome AF: 0.372

GnomAD4 exome AF: 0.391 AC: 571370 AN: 1459982 Hom.: 114256 Cov.: 36 AF XY: 0.393 AC XY: 285246 AN XY: 726350

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.395

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.385

GnomAD4 genome AF: 0.316 AC: 48010 AN: 152086 Hom.: 8442 Cov.: 33 AF XY: 0.311 AC XY: 23159 AN XY: 74348

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.341

Alfa AF: 0.388 Hom.: 12514

Bravo AF: 0.307

Asia WGS AF: 0.294 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.76

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: rs2593053; hg19: chr15-99500256; COSMIC: COSV51293953;