Genetic Variant IGF1R:c.-40_-33dupTTTTTTTT (chr15-98649525-C-CTTTTTTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_000875.5(IGF1R):c.-40_-33dupTTTTTTTT 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 0.0000080 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00025 ( 1 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:

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ACMG classification

Classification was made for transcript

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

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.000253 (152/601514) while in subpopulation SAS AF = 0.000669 (35/52280). AF 95% confidence interval is 0.000494. There are 1 homozygotes in GnomAdExome4. There are 85 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

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.-40_-33dupTTTTTTTT	5_prime_UTR	Exon 1 of 21	NP_000866.1	P08069
IGF1R	NM_001291858.2		c.-40_-33dupTTTTTTTT	5_prime_UTR	Exon 1 of 21	NP_001278787.1	C9J5X1
IRAIN	NR_126453.2		n.1255_1262dupAAAAAAAA	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.-40_-33dupTTTTTTTT	5_prime_UTR	Exon 1 of 21	ENSP00000497069.1	P08069
IGF1R	ENST00000649865.1		c.-40_-33dupTTTTTTTT	5_prime_UTR	Exon 1 of 21	ENSP00000496919.1	C9J5X1
ENSG00000278022	ENST00000747447.1		n.83+2311_83+2318dupTTTTTTTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000802

AC:

AN:

124648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000178

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000253

AC:

152

AN:

601514

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

320992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13900

American (AMR)

AF:

0.000286

AC:

AN:

24496

Ashkenazi Jewish (ASJ)

AF:

0.000245

AC:

AN:

16324

East Asian (EAS)

AF:

0.000363

AC:

AN:

27560

South Asian (SAS)

AF:

0.000669

AC:

AN:

52280

European-Finnish (FIN)

AF:

0.000110

AC:

AN:

36384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2962

European-Non Finnish (NFE)

AF:

0.000226

AC:

AN:

398548

Other (OTH)

AF:

0.0000688

AC:

AN:

29060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.00000802

AC:

AN:

124648

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

59496

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33690

American (AMR)

AF:

0.00

AC:

AN:

12600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3036

East Asian (EAS)

AF:

0.00

AC:

AN:

4022

South Asian (SAS)

AF:

0.00

AC:

AN:

3920

European-Finnish (FIN)

AF:

0.000178

AC:

AN:

5624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59060

Other (OTH)

AF:

0.00

AC:

AN:

1672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

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15-98649525-CTTTTTTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over