rs6953668

Variant names:

• chr7-45916276-G-A
• rs6953668
• NM_000598.5:c.750+272C>T

Variant summary

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

The NM_000598.5(IGFBP3):​c.750+272C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 152,270 control chromosomes in the GnomAD database, including 122 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 0.026 (122 hom., cov: 32)
• Consequence: IGFBP3 NM_000598.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.750+272C>T		intron_variant	Intron 3 of 4	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.768+272C>T		intron_variant	Intron 3 of 4		NP_001013416.1
IGFBP3	XM_047420325.1	c.750+272C>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.750+272C>T		intron_variant	Intron 3 of 4	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes AF: 0.0257 AC: 3903 AN: 152152 Hom.: 120 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.0746

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00467

Gnomad OTH AF: 0.0349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0258 AC: 3923 AN: 152270 Hom.: 122 Cov.: 32 AF XY: 0.0258 AC XY: 1923 AN XY: 74462

African (AFR) AF: 0.0649 AC: 2696 AN: 41536

American (AMR) AF: 0.0197 AC: 302 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3466

East Asian (EAS) AF: 0.0750 AC: 388 AN: 5176

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4822

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10618

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00467 AC: 318 AN: 68026

Other (OTH) AF: 0.0345 AC: 73 AN: 2114

Alfa AF: 0.0132 Hom.: 37

Bravo AF: 0.0287

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		-0.13
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: rs6953668; hg19: chr7-45955875;