rs3743251

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000875.5(IGF1R):​c.*3458G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 233,166 control chromosomes in the GnomAD database, including 3,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1903 hom., cov: 33)
Exomes 𝑓: 0.18 ( 1450 hom. )

Consequence

IGF1R
NM_000875.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.118
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 15-98960900-G-A is Benign according to our data. Variant chr15-98960900-G-A is described in ClinVar as [Benign]. Clinvar id is 317557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IGF1RNM_000875.5 linkc.*3458G>A 3_prime_UTR_variant Exon 21 of 21 ENST00000650285.1 NP_000866.1 P08069

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IGF1RENST00000650285.1 linkc.*3458G>A 3_prime_UTR_variant Exon 21 of 21 NM_000875.5 ENSP00000497069.1 P08069
IGF1RENST00000649865.1 linkc.*3458G>A 3_prime_UTR_variant Exon 21 of 21 ENSP00000496919.1 C9J5X1
SYNM-AS1ENST00000559468.1 linkn.348+5089C>T intron_variant Intron 3 of 3 4

Frequencies

GnomAD3 genomes
AF:
0.150
AC:
22753
AN:
151386
Hom.:
1906
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0994
Gnomad AMI
AF:
0.189
Gnomad AMR
AF:
0.203
Gnomad ASJ
AF:
0.189
Gnomad EAS
AF:
0.380
Gnomad SAS
AF:
0.201
Gnomad FIN
AF:
0.150
Gnomad MID
AF:
0.196
Gnomad NFE
AF:
0.145
Gnomad OTH
AF:
0.158
GnomAD4 exome
AF:
0.176
AC:
14382
AN:
81670
Hom.:
1450
Cov.:
0
AF XY:
0.175
AC XY:
6590
AN XY:
37672
show subpopulations
Gnomad4 AFR exome
AF:
0.0949
Gnomad4 AMR exome
AF:
0.197
Gnomad4 ASJ exome
AF:
0.192
Gnomad4 EAS exome
AF:
0.336
Gnomad4 SAS exome
AF:
0.195
Gnomad4 FIN exome
AF:
0.101
Gnomad4 NFE exome
AF:
0.146
Gnomad4 OTH exome
AF:
0.160
GnomAD4 genome
AF:
0.150
AC:
22746
AN:
151496
Hom.:
1903
Cov.:
33
AF XY:
0.155
AC XY:
11481
AN XY:
74038
show subpopulations
Gnomad4 AFR
AF:
0.0992
Gnomad4 AMR
AF:
0.203
Gnomad4 ASJ
AF:
0.189
Gnomad4 EAS
AF:
0.380
Gnomad4 SAS
AF:
0.201
Gnomad4 FIN
AF:
0.150
Gnomad4 NFE
AF:
0.145
Gnomad4 OTH
AF:
0.156
Alfa
AF:
0.150
Hom.:
1642
Bravo
AF:
0.151
Asia WGS
AF:
0.244
AC:
848
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Growth delay due to insulin-like growth factor I resistance Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
3.2
DANN
Benign
0.60

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: rs3743251; hg19: chr15-99504129; COSMIC: COSV51269833; COSMIC: COSV51269833; API