rs2854747

Variant names:

• chr7-45920318-G-A
• rs2854747
• NM_000598.5:c.403+420C>T

Variant summary

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

The NM_000598.5(IGFBP3):​c.403+420C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 192,158 control chromosomes in the GnomAD database, including 33,418 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 0.59 (26248 hom., cov: 31)
  • Exomes 𝑓: 0.58 (7170 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407

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 (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.403+420C>T		intron_variant	Intron 1 of 4	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.421+402C>T		intron_variant	Intron 1 of 4		NP_001013416.1
IGFBP3	XM_047420325.1	c.403+420C>T		intron_variant	Intron 1 of 3		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.403+420C>T		intron_variant	Intron 1 of 4	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes AF: 0.587 AC: 88727 AN: 151104 Hom.: 26245 Cov.: 31

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.560

GnomAD4 exome AF: 0.582 AC: 23820 AN: 40938 Hom.: 7170 Cov.: 0 AF XY: 0.583 AC XY: 11989 AN XY: 20560

Gnomad4 AFR exome AF: 0.606

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.766

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.587 AC: 88763 AN: 151220 Hom.: 26248 Cov.: 31 AF XY: 0.581 AC XY: 42847 AN XY: 73802

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.589

Gnomad4 OTH AF: 0.555

Alfa AF: 0.585 Hom.: 5435

Bravo AF: 0.583

Asia WGS AF: 0.565 AC: 1965 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	7.7
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2854747; hg19: chr7-45959917;