rs10255707

Positions:

• chr7-45915093-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000598.5(IGFBP3):​c.751-148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 888,058 control chromosomes in the GnomAD database, including 277,786 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 0.81 (50743 hom., cov: 33)
  • Exomes 𝑓: 0.78 (227043 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

Genes affected

IGFBP3 (HGNC:5472): (insulin like growth factor binding protein 3) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.751-148A>G		intron_variant		ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.769-148A>G		intron_variant			NP_001013416.1
IGFBP3	XM_047420325.1	c.751-148A>G		intron_variant			XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.751-148A>G		intron_variant		5	NM_000598.5	ENSP00000477772	P4

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123046 AN: 152084 Hom.: 50693 Cov.: 33

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.823

GnomAD4 exome AF: 0.781 AC: 574615 AN: 735856 Hom.: 227043 Cov.: 10 AF XY: 0.784 AC XY: 296102 AN XY: 377774

Gnomad4 AFR exome AF: 0.944

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.896

Gnomad4 EAS exome AF: 0.866

Gnomad4 SAS exome AF: 0.809

Gnomad4 FIN exome AF: 0.660

Gnomad4 NFE exome AF: 0.782

Gnomad4 OTH exome AF: 0.799

GnomAD4 genome AF: 0.809 AC: 123145 AN: 152202 Hom.: 50743 Cov.: 33 AF XY: 0.800 AC XY: 59502 AN XY: 74378

Gnomad4 AFR AF: 0.940

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.826

Alfa AF: 0.794 Hom.: 9923

Bravo AF: 0.812

Asia WGS AF: 0.816 AC: 2839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.98
DANN	Benign	0.46

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

Other links and lift over

dbSNP: rs10255707; hg19: chr7-45954692;