rs2453837

Variant names:

• chr7-45916451-G-A
• rs2453837
• NM_000598.5:c.750+97C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000598.5(IGFBP3):​c.750+97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00174 in 1,295,998 control chromosomes in the GnomAD database, including 27 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 0.0085 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00084 (12 hom.)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.950
• Publications: 1 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=-0.81).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00853 (1300/152338) while in subpopulation AFR AF = 0.03 (1246/41572). AF 95% confidence interval is 0.0286. There are 15 homozygotes in GnomAd4. There are 604 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 gene

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.750+97C>T		intron	N/A	NP_000589.2
	IGFBP3	NM_001013398.2		c.768+97C>T		intron	N/A	NP_001013416.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.750+97C>T		intron	N/A	ENSP00000477772.2
	IGFBP3	ENST00000908406.1		c.840+97C>T		intron	N/A	ENSP00000578465.1
	IGFBP3	ENST00000381083.9	TSL:5	c.768+97C>T		intron	N/A	ENSP00000370473.4

Frequencies

GnomAD3 genomes AF: 0.00853 AC: 1299 AN: 152220 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.000838 AC: 958 AN: 1143660 Hom.: 12 AF XY: 0.000720 AC XY: 412 AN XY: 572012

African (AFR) AF: 0.0278 AC: 753 AN: 27128

American (AMR) AF: 0.00142 AC: 58 AN: 40702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20922

East Asian (EAS) AF: 0.00 AC: 0 AN: 35874

South Asian (SAS) AF: 0.0000279 AC: 2 AN: 71650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45250

Middle Eastern (MID) AF: 0.000574 AC: 2 AN: 3486

European-Non Finnish (NFE) AF: 0.0000329 AC: 28 AN: 850338

Other (OTH) AF: 0.00238 AC: 115 AN: 48310

GnomAD4 genome AF: 0.00853 AC: 1300 AN: 152338 Hom.: 15 Cov.: 32 AF XY: 0.00811 AC XY: 604 AN XY: 74506

African (AFR) AF: 0.0300 AC: 1246 AN: 41572

American (AMR) AF: 0.00242 AC: 37 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68040

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00728 Hom.: 1

Bravo AF: 0.00967

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.47
PhyloP100		0.95
Mutation Taster		=100/0	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

dbSNP: rs2453837; hg19: chr7-45956050;