7-45921672-G-A

Variant names:

• chr7-45921672-G-A
• rs11765572
• ENST00000448817.1:c.28C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448817.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000448817.1	TSL:4	c.28C>T	p.Arg10*	stop_gained	Exon 1 of 3	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

GnomAD2 exomes AF: 0.0826 AC: 10616 AN: 128564 AF XY: 0.0830

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 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

African (AFR) AF: 0.0731 AC: 596 AN: 8148

American (AMR) AF: 0.0470 AC: 1246 AN: 26532

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 1130 AN: 10714

East Asian (EAS) AF: 0.000675 AC: 6 AN: 8894

South Asian (SAS) AF: 0.0532 AC: 3104 AN: 58344

European-Finnish (FIN) AF: 0.125 AC: 1635 AN: 13126

Middle Eastern (MID) AF: 0.0605 AC: 168 AN: 2776

European-Non Finnish (NFE) AF: 0.131 AC: 20801 AN: 158712

Other (OTH) AF: 0.101 AC: 1440 AN: 14232

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

African (AFR) AF: 0.0747 AC: 3103 AN: 41558

American (AMR) AF: 0.0678 AC: 1037 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5180

South Asian (SAS) AF: 0.0479 AC: 231 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1379 AN: 10612

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9038 AN: 67996

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.108 Hom.: 292

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 v4.9

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
PhyloP100		-2.0
GERP RS		-4.7
PromoterAI		-0.013	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11765572; hg19: chr7-45961271;