rs9282714

Positions:

• chr15-98960461-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000875.5(IGF1R):​c.*3020dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 233,010 control chromosomes in the GnomAD database, including 5,056 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3379 hom., cov: 28)
  • Exomes 𝑓: 0.19 (1677 hom.)
• Consequence: IGF1R NM_000875.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.669

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 -10 ACMG points.

• BP6: Variant 15-98960461-A-AT is Benign according to our data. Variant chr15-98960461-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 317544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5	c.*3020dup		3_prime_UTR_variant	21/21	ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGF1R	ENST00000650285.1	c.*3020dup		3_prime_UTR_variant	21/21		NM_000875.5	P4
SYNM-AS1	ENST00000559468.1	n.348+5527_348+5528insA		intron_variant, non_coding_transcript_variant		4
IGF1R	ENST00000649865.1	c.*3020dup		3_prime_UTR_variant	21/21			A1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31141 AN: 152002 Hom.: 3375 Cov.: 28

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0237

Gnomad SAS AF: 0.0737

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.192 AC: 15510 AN: 80890 Hom.: 1677 Cov.: 0 AF XY: 0.191 AC XY: 7108 AN XY: 37182

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.165

Gnomad4 EAS exome AF: 0.0258

Gnomad4 SAS exome AF: 0.0824

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.236

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.205 AC: 31157 AN: 152120 Hom.: 3379 Cov.: 28 AF XY: 0.200 AC XY: 14871 AN XY: 74366

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0238

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.189

Alfa AF: 0.0833 Hom.: 133

Bravo AF: 0.200

Asia WGS AF: 0.0880 AC: 309 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Growth delay due to insulin-like growth factor I resistance Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs397824885; hg19: chr15-99503690;