7-45921672-G-A

Position:

• chr7-45921672-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000448817.1(IGFBP3):​c.28C>T​(p.Arg10*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 453,732 control chromosomes in the GnomAD database, including 2,775 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 0.10 (908 hom., cov: 33)
  • Exomes 𝑓: 0.10 (1867 hom.)
• Consequence: IGFBP3 ENST00000448817.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.45921672G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000448817.1	c.28C>T	p.Arg10*	stop_gained	1/3	4		ENSP00000389668.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15406 AN: 152136 Hom.: 908 Cov.: 33

Gnomad AFR AF: 0.0745

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0851

GnomAD3 exomes AF: 0.0826 AC: 10616 AN: 128564 Hom.: 578 AF XY: 0.0830 AC XY: 5807 AN XY: 69974

Gnomad AFR exome AF: 0.0697

Gnomad AMR exome AF: 0.0462

Gnomad ASJ exome AF: 0.100

Gnomad EAS exome AF: 0.00102

Gnomad SAS exome AF: 0.0509

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.0930

GnomAD4 exome AF: 0.0999 AC: 30126 AN: 301478 Hom.: 1867 Cov.: 0 AF XY: 0.0967 AC XY: 16613 AN XY: 171790

Gnomad4 AFR exome AF: 0.0731

Gnomad4 AMR exome AF: 0.0470

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.000675

Gnomad4 SAS exome AF: 0.0532

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.101 AC: 15423 AN: 152254 Hom.: 908 Cov.: 33 AF XY: 0.0990 AC XY: 7369 AN XY: 74454

Gnomad4 AFR AF: 0.0747

Gnomad4 AMR AF: 0.0678

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0479

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.0842

Alfa AF: 0.121 Hom.: 255

Bravo AF: 0.0946

TwinsUK AF: 0.130 AC: 482

ALSPAC AF: 0.124 AC: 478

ExAC AF: 0.0712 AC: 1348

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.86	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.95
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0067	N
GERP RS		-4.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11765572; hg19: chr7-45961271;