rs6670

Positions:

• chr7-45912655-T-A

Variant summary

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

The NM_000598.5(IGFBP3):​c.*1195A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,606 control chromosomes in the GnomAD database, including 2,946 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 (2937 hom., cov: 32)
  • Exomes 𝑓: 0.16 (9 hom.)
• Consequence: IGFBP3 NM_000598.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP3	NM_000598.5	c.*1195A>T		3_prime_UTR_variant	5/5	ENST00000613132.5
IGFBP3	NM_001013398.2	c.*1195A>T		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP3	ENST00000613132.5	c.*1195A>T		3_prime_UTR_variant	5/5	5	NM_000598.5	P4
IGFBP3	ENST00000381083.9	c.*1195A>T		3_prime_UTR_variant	5/5	5		A1
IGFBP3	ENST00000381086.9	c.*1195A>T		3_prime_UTR_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27877 AN: 152050 Hom.: 2938 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.162 AC: 71 AN: 438 Hom.: 9 Cov.: 0 AF XY: 0.173 AC XY: 46 AN XY: 266

Gnomad4 FIN exome AF: 0.162

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.183 AC: 27882 AN: 152168 Hom.: 2937 Cov.: 32 AF XY: 0.183 AC XY: 13579 AN XY: 74374

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.0212

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.185

Alfa AF: 0.185 Hom.: 334

Bravo AF: 0.176

Asia WGS AF: 0.225 AC: 784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.77

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: rs6670; hg19: chr7-45952254;