rs13241830

Variant names:

• chr7-45921459-G-A
• rs13241830
• ENST00000448817.1:c.73+168C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	NM_000598.5	MANE Select	c.-319C>T		upstream_gene	N/A	NP_000589.2	P17936-1
	IGFBP3	NM_001013398.2		c.-319C>T		upstream_gene	N/A	NP_001013416.1	P17936-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000448817.1	TSL:4	c.73+168C>T		intron	N/A	ENSP00000389668.1	C9JMX4
	IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.-319C>T		upstream_gene	N/A	ENSP00000477772.2	P17936-1
	IGFBP3	ENST00000908406.1		c.-319C>T		upstream_gene	N/A	ENSP00000578465.1

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

African (AFR) AF: 0.278 AC: 11520 AN: 41484

American (AMR) AF: 0.241 AC: 3686 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1220 AN: 3466

East Asian (EAS) AF: 0.0344 AC: 176 AN: 5118

South Asian (SAS) AF: 0.334 AC: 1612 AN: 4824

European-Finnish (FIN) AF: 0.255 AC: 2697 AN: 10586

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22000 AN: 67924

Other (OTH) AF: 0.311 AC: 654 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.7
DANN	Benign	0.93
PhyloP100		-0.13
PromoterAI		-0.046	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs13241830;

hg19: chr7-45961058;