7-45914213-G-T

Variant names:

• chr7-45914213-G-T
• rs2453840
• NM_000598.5:c.*16-379C>A

Variant summary

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

The NM_000598.5(IGFBP3):​c.*16-379C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 151,920 control chromosomes in the GnomAD database, including 1,866 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 0.15 (1866 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.868
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.*16-379C>A		intron_variant	Intron 4 of 4	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.*16-379C>A		intron_variant	Intron 4 of 4		NP_001013416.1
IGFBP3	XM_047420325.1	c.*607C>A		downstream_gene_variant			XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.*16-379C>A		intron_variant	Intron 4 of 4	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22470 AN: 151802 Hom.: 1865 Cov.: 33

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.142

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.148 AC: 22476 AN: 151920 Hom.: 1866 Cov.: 33 AF XY: 0.145 AC XY: 10764 AN XY: 74262

African (AFR) AF: 0.0968 AC: 4010 AN: 41436

American (AMR) AF: 0.112 AC: 1709 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3470

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5182

South Asian (SAS) AF: 0.0686 AC: 329 AN: 4796

European-Finnish (FIN) AF: 0.193 AC: 2027 AN: 10502

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13092 AN: 67950

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.184 Hom.: 605

Bravo AF: 0.139

Asia WGS AF: 0.0420 AC: 145 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.80
DANN	Benign	0.41
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2453840; hg19: chr7-45953812;