Variant 15-98915979-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate

The NM_000875.5(IGF1R):c.1844T>C(p.Leu615Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,830 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.0000041 ( 1 hom. )

Consequence

IGF1R
NM_000875.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.22

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), IGF1R. . Trascript score misZ 4.6449 (greater than threshold 3.09). GenCC has associacion of gene with growth delay due to insulin-like growth factor I resistance.

BP4

Computational evidence support a benign effect (MetaRNN=0.24581897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF1R	NM_000875.5 linkuse as main transcript	c.1844T>C	p.Leu615Ser	missense_variant	9/21	ENST00000650285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IGF1R	ENST00000650285.1 linkuse as main transcript	c.1844T>C	p.Leu615Ser	missense_variant	9/21		NM_000875.5	P4
IGF1R	ENST00000559925.5 linkuse as main transcript	n.1844T>C		non_coding_transcript_exon_variant	9/10	1
IGF1R	ENST00000649865.1 linkuse as main transcript	c.1844T>C	p.Leu615Ser	missense_variant	9/21			A1
IGF1R	ENST00000560144.1 linkuse as main transcript	c.108-35T>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251490

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.66

D;.;D;.

Eigen

Benign

0.15

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.69

.;.;T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.25

T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.5

M;.;M;.

MutationTaster

Benign

0.95

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.8

.;.;N;N

REVEL

Benign

0.22

Sift

Benign

0.098

.;.;T;T

Sift4G

Benign

0.66

.;.;T;T

Polyphen

0.73

P;P;P;P

Vest4

0.50, 0.78

MutPred

0.50

Gain of disorder (P = 0.0024);Gain of disorder (P = 0.0024);Gain of disorder (P = 0.0024);Gain of disorder (P = 0.0024);

MVP

0.77

MPC

1.3

ClinPred

0.34

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over