chr15-98801694-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000875.5(IGF1R):​c.641-89631G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,236 control chromosomes in the GnomAD database, including 51,690 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: 𝑓 0.82 ( 51690 hom., cov: 34)

Consequence

IGF1R
NM_000875.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.69
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGF1RNM_000875.5 linkuse as main transcriptc.641-89631G>A intron_variant ENST00000650285.1 NP_000866.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGF1RENST00000650285.1 linkuse as main transcriptc.641-89631G>A intron_variant NM_000875.5 ENSP00000497069 P4

Frequencies

GnomAD3 genomes
AF:
0.819
AC:
124546
AN:
152118
Hom.:
51667
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.676
Gnomad AMI
AF:
0.894
Gnomad AMR
AF:
0.838
Gnomad ASJ
AF:
0.838
Gnomad EAS
AF:
0.854
Gnomad SAS
AF:
0.831
Gnomad FIN
AF:
0.909
Gnomad MID
AF:
0.741
Gnomad NFE
AF:
0.882
Gnomad OTH
AF:
0.814
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.819
AC:
124609
AN:
152236
Hom.:
51690
Cov.:
34
AF XY:
0.818
AC XY:
60888
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.676
Gnomad4 AMR
AF:
0.838
Gnomad4 ASJ
AF:
0.838
Gnomad4 EAS
AF:
0.854
Gnomad4 SAS
AF:
0.830
Gnomad4 FIN
AF:
0.909
Gnomad4 NFE
AF:
0.882
Gnomad4 OTH
AF:
0.815
Alfa
AF:
0.839
Hom.:
6980
Bravo
AF:
0.807
Asia WGS
AF:
0.831
AC:
2887
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.0030
DANN
Benign
0.35

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

LitVar

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

Other links and lift over

dbSNP: rs907807; hg19: chr15-99344923; API