Genetic Variant IGF1R:c.-50_-33dupTTTTTTTTTTTTTTTTTT (chr15-98649525-C-CTTTTTTTTTTTTTTTTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000875.5(IGF1R):c.-50_-33dupTTTTTTTTTTTTTTTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00015 ( 2 hom. )

Consequence

IGF1R
NM_000875.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.295

Publications

2 publications found

Variant links:

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]

IGF1R links:

IRAIN (HGNC:50365): (IGF1R antisense imprinted non-protein coding RNA) This gene expresses a long non-coding RNA in antisense to the insulin-like growth factor type I receptor (IGF1R) gene. This transcript is imprinted and expressed from the paternal allele. It interacts with chromatin and may promote long-range DNA interactions that influence the regulation of gene expression. [provided by RefSeq, Nov 2015]

IRAIN links:

ENSG00000278022 (HGNC:):

ENSG00000278022 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000875.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGF1R	NM_000875.5	MANE Select	c.-50_-33dupTTTTTTTTTTTTTTTTTT	5_prime_UTR	Exon 1 of 21	NP_000866.1	P08069
IGF1R	NM_001291858.2		c.-50_-33dupTTTTTTTTTTTTTTTTTT	5_prime_UTR	Exon 1 of 21	NP_001278787.1	C9J5X1
IRAIN	NR_126453.2		n.1245_1262dupAAAAAAAAAAAAAAAAAA	non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGF1R	ENST00000650285.1	MANE Select	c.-50_-33dupTTTTTTTTTTTTTTTTTT	5_prime_UTR	Exon 1 of 21	ENSP00000497069.1	P08069
IGF1R	ENST00000649865.1		c.-50_-33dupTTTTTTTTTTTTTTTTTT	5_prime_UTR	Exon 1 of 21	ENSP00000496919.1	C9J5X1
ENSG00000278022	ENST00000747447.1		n.83+2301_83+2318dupTTTTTTTTTTTTTTTTTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000458

AC:

AN:

124582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000891

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000238

Gnomad ASJ

AF:

0.000660

Gnomad EAS

AF:

0.000748

Gnomad SAS

AF:

0.000766

Gnomad FIN

AF:

0.000178

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000712

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000151

AC:

AN:

601552

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

AN XY:

321010

show subpopulations

African (AFR)

AF:

0.0000719

AC:

AN:

13902

American (AMR)

AF:

0.0000816

AC:

AN:

24498

Ashkenazi Jewish (ASJ)

AF:

0.000245

AC:

AN:

16324

East Asian (EAS)

AF:

0.000109

AC:

AN:

27560

South Asian (SAS)

AF:

0.000478

AC:

AN:

52282

European-Finnish (FIN)

AF:

0.000137

AC:

AN:

36386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2964

European-Non Finnish (NFE)

AF:

0.000125

AC:

AN:

398572

Other (OTH)

AF:

0.0000344

AC:

AN:

29064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000458

AC:

AN:

124590

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

AN XY:

59492

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000889

AC:

AN:

33728

American (AMR)

AF:

0.000238

AC:

AN:

12606

Ashkenazi Jewish (ASJ)

AF:

0.000660

AC:

AN:

3030

East Asian (EAS)

AF:

0.000750

AC:

AN:

4002

South Asian (SAS)

AF:

0.000770

AC:

AN:

3894

European-Finnish (FIN)

AF:

0.000178

AC:

AN:

5624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.000712

AC:

AN:

59014

Other (OTH)

AF:

0.00

AC:

AN:

1684

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.345

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over