rs11630259

Variant summary

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

The NM_000875.5(IGF1R):​c.641-3606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 152,198 control chromosomes in the GnomAD database, including 4,894 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 0.25 ( 4894 hom., cov: 33)

Consequence

IGF1R
NM_000875.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.196
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=-0.9).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IGF1RNM_000875.5 linkuse as main transcriptc.641-3606T>C intron_variant ENST00000650285.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IGF1RENST00000650285.1 linkuse as main transcriptc.641-3606T>C intron_variant NM_000875.5 P4
ENST00000558736.1 linkuse as main transcriptn.69+5748A>G intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.246
AC:
37351
AN:
152080
Hom.:
4896
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.183
Gnomad AMI
AF:
0.219
Gnomad AMR
AF:
0.217
Gnomad ASJ
AF:
0.355
Gnomad EAS
AF:
0.135
Gnomad SAS
AF:
0.350
Gnomad FIN
AF:
0.277
Gnomad MID
AF:
0.421
Gnomad NFE
AF:
0.279
Gnomad OTH
AF:
0.274
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.245
AC:
37354
AN:
152198
Hom.:
4894
Cov.:
33
AF XY:
0.245
AC XY:
18221
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.183
Gnomad4 AMR
AF:
0.217
Gnomad4 ASJ
AF:
0.355
Gnomad4 EAS
AF:
0.136
Gnomad4 SAS
AF:
0.349
Gnomad4 FIN
AF:
0.277
Gnomad4 NFE
AF:
0.279
Gnomad4 OTH
AF:
0.271
Alfa
AF:
0.269
Hom.:
3424
Bravo
AF:
0.236
Asia WGS
AF:
0.240
AC:
835
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
1.6
DANN
Benign
0.36

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: rs11630259; hg19: chr15-99430948; API