Genetic Variant IGF1R:c.-36_-33dupTTTT (chr15-98649525-C-CTTTT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_000875.5(IGF1R):c.-36_-33dupTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0012 ( 5 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: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000128 (16/124646) while in subpopulation AFR AF = 0.000267 (9/33730). AF 95% confidence interval is 0.000139. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 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.-36_-33dupTTTT	5_prime_UTR	Exon 1 of 21	NP_000866.1	P08069
IGF1R	NM_001291858.2		c.-36_-33dupTTTT	5_prime_UTR	Exon 1 of 21	NP_001278787.1	C9J5X1
IRAIN	NR_126453.2		n.1259_1262dupAAAA	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.-36_-33dupTTTT	5_prime_UTR	Exon 1 of 21	ENSP00000497069.1	P08069
IGF1R	ENST00000649865.1		c.-36_-33dupTTTT	5_prime_UTR	Exon 1 of 21	ENSP00000496919.1	C9J5X1
ENSG00000278022	ENST00000747447.1		n.83+2315_83+2318dupTTTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000128

AC:

AN:

124638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000267

Gnomad AMI

AF:

0.00126

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000102

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00123

AC:

739

AN:

601298

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

401

AN XY:

320872

show subpopulations

African (AFR)

AF:

0.000432

AC:

AN:

13896

American (AMR)

AF:

0.00159

AC:

AN:

24488

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

16320

East Asian (EAS)

AF:

0.00134

AC:

AN:

27534

South Asian (SAS)

AF:

0.00306

AC:

160

AN:

52250

European-Finnish (FIN)

AF:

0.00110

AC:

AN:

36376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2964

European-Non Finnish (NFE)

AF:

0.00100

AC:

400

AN:

398418

Other (OTH)

AF:

0.00131

AC:

AN:

29052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000128

AC:

AN:

124646

Hom.:

Cov.:

AF XY:

0.000151

AC XY:

AN XY:

59516

show subpopulations

African (AFR)

AF:

0.000267

AC:

AN:

33730

American (AMR)

AF:

0.00

AC:

AN:

12608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3036

East Asian (EAS)

AF:

0.00

AC:

AN:

4010

South Asian (SAS)

AF:

0.00

AC:

AN:

3896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

214

European-Non Finnish (NFE)

AF:

0.000102

AC:

AN:

59050

Other (OTH)

AF:

0.00

AC:

AN:

1684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

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

Alfa

AF:

0.00

Hom.:

328

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.29

Mutation Taster

=300/0

polymorphism

(source)

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