15-98960461-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000875.5(IGF1R):​c.*3020dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 233,010 control chromosomes in the GnomAD database, including 5,056 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.20 ( 3379 hom., cov: 28)
Exomes 𝑓: 0.19 ( 1677 hom. )

Consequence

IGF1R
NM_000875.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.669
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)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
Variant 15-98960461-A-AT is Benign according to our data. Variant chr15-98960461-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 317544.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IGF1RNM_000875.5 linkuse as main transcriptc.*3020dup 3_prime_UTR_variant 21/21 ENST00000650285.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IGF1RENST00000650285.1 linkuse as main transcriptc.*3020dup 3_prime_UTR_variant 21/21 NM_000875.5 P4
SYNM-AS1ENST00000559468.1 linkuse as main transcriptn.348+5527_348+5528insA intron_variant, non_coding_transcript_variant 4
IGF1RENST00000649865.1 linkuse as main transcriptc.*3020dup 3_prime_UTR_variant 21/21 A1

Frequencies

GnomAD3 genomes
AF:
0.205
AC:
31141
AN:
152002
Hom.:
3375
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.177
Gnomad AMI
AF:
0.289
Gnomad AMR
AF:
0.177
Gnomad ASJ
AF:
0.166
Gnomad EAS
AF:
0.0237
Gnomad SAS
AF:
0.0737
Gnomad FIN
AF:
0.260
Gnomad MID
AF:
0.120
Gnomad NFE
AF:
0.244
Gnomad OTH
AF:
0.191
GnomAD4 exome
AF:
0.192
AC:
15510
AN:
80890
Hom.:
1677
Cov.:
0
AF XY:
0.191
AC XY:
7108
AN XY:
37182
show subpopulations
Gnomad4 AFR exome
AF:
0.169
Gnomad4 AMR exome
AF:
0.182
Gnomad4 ASJ exome
AF:
0.165
Gnomad4 EAS exome
AF:
0.0258
Gnomad4 SAS exome
AF:
0.0824
Gnomad4 FIN exome
AF:
0.265
Gnomad4 NFE exome
AF:
0.236
Gnomad4 OTH exome
AF:
0.193
GnomAD4 genome
AF:
0.205
AC:
31157
AN:
152120
Hom.:
3379
Cov.:
28
AF XY:
0.200
AC XY:
14871
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.177
Gnomad4 AMR
AF:
0.178
Gnomad4 ASJ
AF:
0.166
Gnomad4 EAS
AF:
0.0238
Gnomad4 SAS
AF:
0.0742
Gnomad4 FIN
AF:
0.260
Gnomad4 NFE
AF:
0.244
Gnomad4 OTH
AF:
0.189
Alfa
AF:
0.0833
Hom.:
133
Bravo
AF:
0.200
Asia WGS
AF:
0.0880
AC:
309
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Growth delay due to insulin-like growth factor I resistance Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs397824885; hg19: chr15-99503690; API