rs1065781

Positions:

• chr7-45891798-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000596.4(IGFBP1):​c.520-134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 746,476 control chromosomes in the GnomAD database, including 98 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 0.016 (70 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (28 hom.)
• Consequence: IGFBP1 NM_000596.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP1	NM_000596.4	c.520-134C>T		intron_variant		ENST00000275525.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP1	ENST00000275525.8	c.520-134C>T		intron_variant		1	NM_000596.4	P4
IGFBP1	ENST00000457280.5	c.520-134C>T		intron_variant		5		A2
IGFBP1	ENST00000468955.1	c.519+1081C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2476 AN: 152226 Hom.: 69 Cov.: 33

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00183 AC: 1085 AN: 594132 Hom.: 28 AF XY: 0.00149 AC XY: 460 AN XY: 308636

Gnomad4 AFR exome AF: 0.0570

Gnomad4 AMR exome AF: 0.00393

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000166

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000683

Gnomad4 OTH exome AF: 0.00367

GnomAD4 genome AF: 0.0163 AC: 2481 AN: 152344 Hom.: 70 Cov.: 33 AF XY: 0.0155 AC XY: 1156 AN XY: 74504

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.00601

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0130 Hom.: 2

Bravo AF: 0.0191

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.84
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs1065781; hg19: chr7-45931397;