chr7-45915093-T-A

Variant names:

• chr7-45915093-T-A
• rs10255707
• NM_000598.5:c.751-148A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000598.5(IGFBP3):​c.751-148A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000136 in 737,262 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.751-148A>T		intron_variant	Intron 3 of 4	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.769-148A>T		intron_variant	Intron 3 of 4		NP_001013416.1
IGFBP3	XM_047420325.1	c.751-148A>T		intron_variant	Intron 3 of 3		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.751-148A>T		intron_variant	Intron 3 of 4	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000136 AC: 1 AN: 737262 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 378476

African (AFR) AF: 0.00 AC: 0 AN: 18598

American (AMR) AF: 0.00 AC: 0 AN: 26620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15920

East Asian (EAS) AF: 0.00 AC: 0 AN: 32132

South Asian (SAS) AF: 0.00 AC: 0 AN: 56636

European-Finnish (FIN) AF: 0.0000331 AC: 1 AN: 30248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3362

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 518560

Other (OTH) AF: 0.00 AC: 0 AN: 35186

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.73
DANN	Benign	0.60
PhyloP100		-1.5

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: rs10255707; hg19: chr7-45954692;