rs3793344

Variant names:

• chr7-45889296-A-G
• rs3793344
• NM_000596.4:c.349+295A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-45889296-A-G
• chr7-45889296-A-T

Variant summary

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

The NM_000596.4(IGFBP1):​c.349+295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,062 control chromosomes in the GnomAD database, including 11,799 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 0.39 (11799 hom., cov: 33)
• Consequence: IGFBP1 NM_000596.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 5 publications found

Genes affected

IGFBP1 (HGNC:5469): (insulin like growth factor binding protein 1) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP N-terminal domain and a thyroglobulin type-I domain. The encoded protein, mainly expressed in the liver, circulates in the plasma and binds both insulin-like growth factors (IGFs) I and II, prolonging their half-lives and altering their interaction with cell surface receptors. This protein is important in cell migration and metabolism. Low levels of this protein may be associated with impaired glucose tolerance, vascular disease and hypertension in human patients. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP1	NM_000596.4	c.349+295A>G		intron_variant	Intron 1 of 3	ENST00000275525.8	NP_000587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP1	ENST00000275525.8	c.349+295A>G		intron_variant	Intron 1 of 3	1	NM_000596.4	ENSP00000275525.3
IGFBP1	ENST00000457280.5	c.349+295A>G		intron_variant	Intron 1 of 3	5		ENSP00000413511.1
IGFBP1	ENST00000468955.1	c.349+295A>G		intron_variant	Intron 1 of 2	5		ENSP00000417069.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59247 AN: 151944 Hom.: 11778 Cov.: 33

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.390 AC: 59301 AN: 152062 Hom.: 11799 Cov.: 33 AF XY: 0.385 AC XY: 28636 AN XY: 74320

African (AFR) AF: 0.421 AC: 17488 AN: 41494

American (AMR) AF: 0.373 AC: 5702 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3466

East Asian (EAS) AF: 0.533 AC: 2742 AN: 5140

South Asian (SAS) AF: 0.207 AC: 998 AN: 4822

European-Finnish (FIN) AF: 0.333 AC: 3526 AN: 10602

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26375 AN: 67936

Other (OTH) AF: 0.402 AC: 848 AN: 2112

Alfa AF: 0.236 Hom.: 509

Bravo AF: 0.402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.10
DANN	Benign	0.22
PhyloP100		-1.1
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: rs3793344; hg19: chr7-45928895;