rs35440925

chr7-45915374-G-Cchr7-45915374-G-T

Variant summary

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

The NM_000598.5(IGFBP3):c.751-429C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 175,574 control chromosomes in the GnomAD database, including 3,069 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 0.18 (2614 hom., cov: 33)
  • Exomes 𝑓: 0.19 (455 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP3	NM_000598.5	c.751-429C>G		intron_variant		ENST00000613132.5
IGFBP3	NM_001013398.2	c.769-429C>G		intron_variant
IGFBP3	XM_047420325.1	c.751-429C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP3	ENST00000613132.5	c.751-429C>G		intron_variant		5	NM_000598.5	P4

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27518 AN: 152036 Hom.: 2609 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.187 AC: 4382 AN: 23420 Hom.: 455 Cov.: 0 AF XY: 0.194 AC XY: 2292 AN XY: 11814

Gnomad4 AFR exome AF: 0.175

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.0273

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.181 AC: 27551 AN: 152154 Hom.: 2614 Cov.: 33 AF XY: 0.178 AC XY: 13260 AN XY: 74390

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.218

Alfa AF: 0.0870 Hom.: 104

Bravo AF: 0.180

Asia WGS AF: 0.193 AC: 674 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	0.12
Dann	Benign	0.41

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: rs35440925; hg19: chr7-45954973;