rs5742694

Variant summary

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

The NM_000618.5(IGF1):​c.403-2892G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 151,746 control chromosomes in the GnomAD database, including 44,629 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 0.77 ( 44629 hom., cov: 29)

Consequence

IGF1
NM_000618.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23
Variant links:
Genes affected
IGF1 (HGNC:5464): (insulin like growth factor 1) The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]
LINC02456 (HGNC:53389): (long intergenic non-protein coding RNA 2456)

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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=-0.91).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGF1NM_000618.5 linkuse as main transcriptc.403-2892G>T intron_variant ENST00000337514.11 NP_000609.1
LINC02456XR_007063427.1 linkuse as main transcriptn.815+1227C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGF1ENST00000337514.11 linkuse as main transcriptc.403-2892G>T intron_variant 1 NM_000618.5 ENSP00000337612 P1P05019-2
LINC02456ENST00000704346.1 linkuse as main transcriptn.1067-17613C>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.766
AC:
116213
AN:
151628
Hom.:
44593
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.770
Gnomad AMI
AF:
0.909
Gnomad AMR
AF:
0.835
Gnomad ASJ
AF:
0.738
Gnomad EAS
AF:
0.830
Gnomad SAS
AF:
0.730
Gnomad FIN
AF:
0.769
Gnomad MID
AF:
0.729
Gnomad NFE
AF:
0.746
Gnomad OTH
AF:
0.772
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.766
AC:
116300
AN:
151746
Hom.:
44629
Cov.:
29
AF XY:
0.769
AC XY:
56990
AN XY:
74136
show subpopulations
Gnomad4 AFR
AF:
0.770
Gnomad4 AMR
AF:
0.835
Gnomad4 ASJ
AF:
0.738
Gnomad4 EAS
AF:
0.830
Gnomad4 SAS
AF:
0.729
Gnomad4 FIN
AF:
0.769
Gnomad4 NFE
AF:
0.746
Gnomad4 OTH
AF:
0.771
Alfa
AF:
0.750
Hom.:
6257
Bravo
AF:
0.775
Asia WGS
AF:
0.785
AC:
2729
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
3.0
DANN
Benign
0.44

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.

Other links and lift over

dbSNP: rs5742694; hg19: chr12-102799236; COSMIC: COSV61705253; COSMIC: COSV61705253; API