rs2141155101

Variant names:

• chr15-98649613-C-G
• rs2141155101
• NM_000875.5:c.32C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-98649613-C-G
• chr15-98649613-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000875.5(IGF1R):​c.32C>G​(p.Thr11Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T11I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGF1R NM_000875.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60
• Publications: 0 publications found

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]

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]

ENSG00000278022 (HGNC:):

ACMG classification

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=0.20565611).

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.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	NM_000875.5	MANE Select	c.32C>G	p.Thr11Ser	missense	Exon 1 of 21	NP_000866.1	P08069
	IGF1R	NM_001291858.2		c.32C>G	p.Thr11Ser	missense	Exon 1 of 21	NP_001278787.1	C9J5X1
	IRAIN	NR_126453.2		n.1175G>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1R	ENST00000650285.1	MANE Select	c.32C>G	p.Thr11Ser	missense	Exon 1 of 21	ENSP00000497069.1	P08069
	IGF1R	ENST00000559925.5	TSL:1	n.32C>G		non_coding_transcript_exon	Exon 1 of 10
	IGF1R	ENST00000649865.1		c.32C>G	p.Thr11Ser	missense	Exon 1 of 21	ENSP00000496919.1	C9J5X1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.048
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.11
Sift	Benign	0.15	T
Sift4G	Benign	0.33	T
Polyphen		0.0070	B
Vest4		0.27
MutPred		0.31		Loss of helix (P = 0.0041)
MVP		0.70
MPC		0.68
ClinPred		0.65	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.29
gMVP		0.49

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

Other links and lift over

dbSNP: rs2141155101; hg19: chr15-99192842;