rs1039075610

Variant names:

• chr7-45914845-T-C
• NM_000598.5:c.851A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-45914845-T-C
• chr7-45914845-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000598.5(IGFBP3):​c.851A>G​(p.His284Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IGFBP3 NM_000598.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.851A>G	p.His284Arg	missense_variant	Exon 4 of 5	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.869A>G	p.His290Arg	missense_variant	Exon 4 of 5		NP_001013416.1
IGFBP3	XM_047420325.1	c.851A>G	p.His284Arg	missense_variant	Exon 4 of 4		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.851A>G	p.His284Arg	missense_variant	Exon 4 of 5	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461820 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727218

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;T;T;.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	.;.;L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	D;.;D;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.020	D;.;D;D;.
Sift4G	Uncertain	0.048	D;T;D;D;T
Polyphen		0.93	P;.;D;.;.
Vest4		0.52
MutPred		0.47		.;.;Gain of MoRF binding (P = 9e-04);.;.;
MVP		0.86
MPC		0.94
ClinPred		0.96	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.77

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-45954444;