rs9282714

Variant names:

• chr15-98960461-A-AT
• rs397824885
• NM_000875.5:c.*3020dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000650285.1(IGF1R):​c.*3020dupT 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 ENST00000650285.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.669
• Publications: 2 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650285.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	NM_000875.5	MANE Select	c.*3020dupT		3_prime_UTR	Exon 21 of 21	NP_000866.1
	IGF1R	NM_001291858.2		c.*3020dupT		3_prime_UTR	Exon 21 of 21	NP_001278787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.*3020dupT		3_prime_UTR	Exon 21 of 21	ENSP00000497069.1
	IGF1R	ENST00000649865.1		c.*3020dupT		3_prime_UTR	Exon 21 of 21	ENSP00000496919.1
	SYNM-AS1	ENST00000559468.1	TSL:4	n.348+5527dupA		intron	N/A

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

African (AFR) AF: 0.169 AC: 655 AN: 3886

American (AMR) AF: 0.182 AC: 455 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 844 AN: 5116

East Asian (EAS) AF: 0.0258 AC: 294 AN: 11390

South Asian (SAS) AF: 0.0824 AC: 58 AN: 704

European-Finnish (FIN) AF: 0.265 AC: 18 AN: 68

Middle Eastern (MID) AF: 0.171 AC: 84 AN: 492

European-Non Finnish (NFE) AF: 0.236 AC: 11796 AN: 49974

Other (OTH) AF: 0.193 AC: 1306 AN: 6762

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

African (AFR) AF: 0.177 AC: 7343 AN: 41526

American (AMR) AF: 0.178 AC: 2714 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3470

East Asian (EAS) AF: 0.0238 AC: 123 AN: 5172

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4824

European-Finnish (FIN) AF: 0.260 AC: 2750 AN: 10588

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16594 AN: 67944

Other (OTH) AF: 0.189 AC: 398 AN: 2108

Alfa AF: 0.0833 Hom.: 133

Bravo AF: 0.200

Asia WGS AF: 0.0880 AC: 309 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Growth delay due to insulin-like growth factor I resistance (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.67
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: rs397824885; hg19: chr15-99503690; COSMIC: COSV51294282; COSMIC: COSV51294282;