7-45921476-G-T

Variant names:

• chr7-45921476-G-T
• rs2854744
• ENST00000448817.1:c.73+151C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448817.1(IGFBP3):​c.73+151C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,894 control chromosomes in the GnomAD database, including 18,365 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 0.48 (18365 hom., cov: 32)
• Consequence: IGFBP3 ENST00000448817.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• Publications: 193 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.733 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.-336C>A		upstream_gene	N/A	NP_000589.2	P17936-1
	IGFBP3	NM_001013398.2		c.-336C>A		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+151C>A		intron	N/A	ENSP00000389668.1	C9JMX4
	IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.-336C>A		upstream_gene	N/A	ENSP00000477772.2	P17936-1
	IGFBP3	ENST00000908406.1		c.-336C>A		upstream_gene	N/A	ENSP00000578465.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73542 AN: 151776 Hom.: 18369 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.484 AC: 73563 AN: 151894 Hom.: 18365 Cov.: 32 AF XY: 0.480 AC XY: 35634 AN XY: 74236

African (AFR) AF: 0.567 AC: 23514 AN: 41446

American (AMR) AF: 0.378 AC: 5778 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1778 AN: 3466

East Asian (EAS) AF: 0.753 AC: 3815 AN: 5068

South Asian (SAS) AF: 0.443 AC: 2136 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4021 AN: 10578

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30810 AN: 67904

Other (OTH) AF: 0.474 AC: 1001 AN: 2114

Alfa AF: 0.298 Hom.: 675

Bravo AF: 0.490

Asia WGS AF: 0.538 AC: 1870 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		-0.34
PromoterAI		-0.050	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: rs2854744;

hg19: chr7-45961075;