7-45921130-G-A

Variant names:

• chr7-45921130-G-A
• NM_000598.5:c.11C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000598.5(IGFBP3):​c.11C>T​(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000371 in 1,347,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: IGFBP3 NM_000598.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.114
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000598.5. 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.11C>T	p.Ala4Val	missense	Exon 1 of 5	NP_000589.2	P17936-1
	IGFBP3	NM_001013398.2		c.11C>T	p.Ala4Val	missense	Exon 1 of 5	NP_001013416.1	P17936-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.11C>T	p.Ala4Val	missense	Exon 1 of 5	ENSP00000477772.2	P17936-1
	IGFBP3	ENST00000908406.1		c.11C>T	p.Ala4Val	missense	Exon 1 of 6	ENSP00000578465.1
	IGFBP3	ENST00000381083.9	TSL:5	c.11C>T	p.Ala4Val	missense	Exon 1 of 5	ENSP00000370473.4	P17936-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000371 AC: 5 AN: 1347488 Hom.: 0 Cov.: 34 AF XY: 0.00000752 AC XY: 5 AN XY: 664768

African (AFR) AF: 0.00 AC: 0 AN: 27170

American (AMR) AF: 0.00 AC: 0 AN: 32644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23654

East Asian (EAS) AF: 0.00 AC: 0 AN: 31050

South Asian (SAS) AF: 0.00 AC: 0 AN: 76676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4938

European-Non Finnish (NFE) AF: 9.41e-7 AC: 1 AN: 1062168

Other (OTH) AF: 0.0000714 AC: 4 AN: 56018

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.0097	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Benign	0.91
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.19	N
M_CAP	Benign	0.075	D
PhyloP100		0.11
ClinPred		0.26	T
GERP RS		2.5
PromoterAI		-0.043	Neutral
Varity_R		0.072
Mutation Taster		=74/26	polymorphism

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

hg19: chr7-45960729;