rs1065781

Variant names:

• chr7-45891798-C-A
• rs1065781
• NM_000596.4:c.520-134C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-45891798-C-A
• chr7-45891798-C-T

Variant summary

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

The NM_000596.4(IGFBP1):​c.520-134C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000168 in 594,142 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: 0.0000017 (0 hom.)
• Consequence: IGFBP1 NM_000596.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.593
• Publications: 0 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: 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
IGFBP1	NM_000596.4	c.520-134C>A		intron_variant	Intron 2 of 3	ENST00000275525.8	NP_000587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP1	ENST00000275525.8	c.520-134C>A		intron_variant	Intron 2 of 3	1	NM_000596.4	ENSP00000275525.3
IGFBP1	ENST00000457280.5	c.520-134C>A		intron_variant	Intron 2 of 3	5		ENSP00000413511.1
IGFBP1	ENST00000468955.1	c.519+1081C>A		intron_variant	Intron 2 of 2	5		ENSP00000417069.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000168 AC: 1 AN: 594142 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 308638

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 14892

American (AMR) AF: 0.00 AC: 0 AN: 20586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14812

East Asian (EAS) AF: 0.00 AC: 0 AN: 32048

South Asian (SAS) AF: 0.00 AC: 0 AN: 48054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2606

European-Non Finnish (NFE) AF: 0.00000253 AC: 1 AN: 395088

Other (OTH) AF: 0.00 AC: 0 AN: 30794

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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	0.65
DANN	Benign	0.78
PhyloP100		-0.59

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: rs1065781; hg19: chr7-45931397;