rs3110697

Positions:

• chr7-45915430-A-G
• chr7-45915430-A-T

Variant summary

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

The NM_000598.5(IGFBP3):​c.751-485T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 166,420 control chromosomes in the GnomAD database, including 27,750 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 0.58 (25507 hom., cov: 32)
  • Exomes 𝑓: 0.55 (2243 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP3	NM_000598.5	c.751-485T>C		intron_variant		ENST00000613132.5
IGFBP3	NM_001013398.2	c.769-485T>C		intron_variant
IGFBP3	XM_047420325.1	c.751-485T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP3	ENST00000613132.5	c.751-485T>C		intron_variant		5	NM_000598.5	P4

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87525 AN: 151924 Hom.: 25503 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.549 AC: 7887 AN: 14378 Hom.: 2243 AF XY: 0.541 AC XY: 3986 AN XY: 7366

Gnomad4 AFR exome AF: 0.576

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.649

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.498

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.531

GnomAD4 genome AF: 0.576 AC: 87567 AN: 152042 Hom.: 25507 Cov.: 32 AF XY: 0.570 AC XY: 42339 AN XY: 74292

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.549

Alfa AF: 0.573 Hom.: 35380

Bravo AF: 0.574

Asia WGS AF: 0.559 AC: 1945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.44

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: rs3110697; hg19: chr7-45955029;