rs1065781

Variant summary

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

The NM_000596.4(IGFBP1):​c.520-134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 746,476 control chromosomes in the GnomAD database, including 98 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 0.016 ( 70 hom., cov: 33)
Exomes 𝑓: 0.0018 ( 28 hom. )

Consequence

IGFBP1
NM_000596.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.593
Variant links:
Genes affected
IGFBP1 (HGNC:5469): (insulin like growth factor binding protein 1) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP N-terminal domain and a thyroglobulin type-I domain. The encoded protein, mainly expressed in the liver, circulates in the plasma and binds both insulin-like growth factors (IGFs) I and II, prolonging their half-lives and altering their interaction with cell surface receptors. This protein is important in cell migration and metabolism. Low levels of this protein may be associated with impaired glucose tolerance, vascular disease and hypertension in human patients. [provided by RefSeq, Aug 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IGFBP1NM_000596.4 linkuse as main transcriptc.520-134C>T intron_variant ENST00000275525.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IGFBP1ENST00000275525.8 linkuse as main transcriptc.520-134C>T intron_variant 1 NM_000596.4 P4
IGFBP1ENST00000457280.5 linkuse as main transcriptc.520-134C>T intron_variant 5 A2
IGFBP1ENST00000468955.1 linkuse as main transcriptc.519+1081C>T intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0163
AC:
2476
AN:
152226
Hom.:
69
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0567
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00602
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.0105
GnomAD4 exome
AF:
0.00183
AC:
1085
AN:
594132
Hom.:
28
AF XY:
0.00149
AC XY:
460
AN XY:
308636
show subpopulations
Gnomad4 AFR exome
AF:
0.0570
Gnomad4 AMR exome
AF:
0.00393
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000166
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000683
Gnomad4 OTH exome
AF:
0.00367
GnomAD4 genome
AF:
0.0163
AC:
2481
AN:
152344
Hom.:
70
Cov.:
33
AF XY:
0.0155
AC XY:
1156
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0567
Gnomad4 AMR
AF:
0.00601
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.0130
Hom.:
2
Bravo
AF:
0.0191
Asia WGS
AF:
0.00433
AC:
15
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.84
DANN
Benign
0.78

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: rs1065781; hg19: chr7-45931397; API