7-45921459-G-A

Position:

• chr7-45921459-G-A

Variant summary

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

The ENST00000448817.1(IGFBP3):​c.73+168C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,010 control chromosomes in the GnomAD database, including 6,661 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 0.29 (6661 hom., cov: 32)
• Consequence: IGFBP3 ENST00000448817.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000448817.1	c.73+168C>T		intron_variant		4		ENSP00000389668

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43821 AN: 151896 Hom.: 6651 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.304

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 43873 AN: 152010 Hom.: 6661 Cov.: 32 AF XY: 0.284 AC XY: 21107 AN XY: 74312

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.0344

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.311

Alfa AF: 0.324 Hom.: 1035

Bravo AF: 0.283

Asia WGS AF: 0.224 AC: 779 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.7
DANN	Benign	0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13241830; hg19: chr7-45961058;