GeneBe

rs45453791

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000875.5(IGF1R):​c.4065C>G​(p.Asn1355Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. N1355N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

IGF1R
NM_000875.5 missense

Scores

1
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.125

Publications

0 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]
SYNM-AS1 (HGNC:55421): (SYNM antisense RNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19930825).

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

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
IGF1R
NM_000875.5
MANE Select
c.4065C>Gp.Asn1355Lys
missense
Exon 21 of 21NP_000866.1P08069
IGF1R
NM_001291858.2
c.4062C>Gp.Asn1354Lys
missense
Exon 21 of 21NP_001278787.1C9J5X1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
IGF1R
ENST00000650285.1
MANE Select
c.4065C>Gp.Asn1355Lys
missense
Exon 21 of 21ENSP00000497069.1P08069
IGF1R
ENST00000649865.1
c.4062C>Gp.Asn1354Lys
missense
Exon 21 of 21ENSP00000496919.1C9J5X1
SYNM-AS1
ENST00000559468.1
TSL:4
n.349-3015G>C
intron
N/A

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not provided (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.80
D
Eigen
Benign
-0.046
Eigen_PC
Benign
-0.093
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.20
T
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Uncertain
2.3
M
PhyloP100
-0.13
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-3.5
D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0090
D
Polyphen
0.90
P
Vest4
0.22
MutPred
0.32
Gain of methylation at N1355 (P = 0.0098)
MVP
0.80
MPC
0.21
ClinPred
0.98
D
GERP RS
0.62
Varity_R
0.51
gMVP
0.42
Mutation Taster
=21/79
disease causing

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

Other links and lift over

dbSNP: rs45453791; hg19: chr15-99500632; API