Genetic Variant IGF1R:c.*4645C>G (chr15-98962087-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000875.5(IGF1R):c.*4645C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 80,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

IGF1R
NM_000875.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.35

Publications

8 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:

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

SYNM-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF1R	NM_000875.5 link	c.*4645C>G		3_prime_UTR_variant	Exon 21 of 21	ENST00000650285.1	NP_000866.1	P08069

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGF1R	ENST00000650285.1 link	c.*4645C>G	3_prime_UTR_variant	Exon 21 of 21		NM_000875.5	ENSP00000497069.1	P08069
IGF1R	ENST00000649865.1 link	c.*4645C>G	3_prime_UTR_variant	Exon 21 of 21			ENSP00000496919.1	C9J5X1
SYNM-AS1	ENST00000559468.1 link	n.348+3902G>C	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

80980

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

37228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3892

American (AMR)

AF:

0.00

AC:

AN:

2500

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5124

East Asian (EAS)

AF:

0.00

AC:

AN:

11408

South Asian (SAS)

AF:

0.00

AC:

AN:

702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

492

European-Non Finnish (NFE)

AF:

0.0000200

AC:

AN:

50036

Other (OTH)

AF:

0.00

AC:

AN:

6764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.041

(source)

DANN

Benign

0.41

PhyloP100

-2.4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over