4-57110791-C-T

Variant names:

• chr4-57110791-C-T
• rs4075349
• ENST00000499667.6:n.209+821C>T

Variant summary

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

The ENST00000667601.1(ENSG00000287369):​n.245C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,998 control chromosomes in the GnomAD database, including 19,314 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 0.49 (19314 hom., cov: 31)
• Consequence: ENSG00000287369 ENST00000667601.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• Publications: 9 publications found

Genes affected

IGFBP7-AS1 (HGNC:40296): (IGFBP7 antisense RNA 1)

ENSG00000287369 (HGNC:):

IGFBP7 (HGNC:5476): (insulin like growth factor binding protein 7) This gene encodes a member of the insulin-like growth factor (IGF)-binding protein (IGFBP) family. IGFBPs bind IGFs with high affinity, and regulate IGF availability in body fluids and tissues and modulate IGF binding to its receptors. This protein binds IGF-I and IGF-II with relatively low affinity, and belongs to a subfamily of low-affinity IGFBPs. It also stimulates prostacyclin production and cell adhesion. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, and one variant has been associated with retinal arterial macroaneurysm (PMID:21835307). [provided by RefSeq, Dec 2011]

IGFBP7 Gene-Disease associations (from GenCC):

• familial retinal arterial macroaneurysm

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000667601.1. 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
	IGFBP7-AS1	NR_034081.1		n.209+821C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP7-AS1	ENST00000499667.6	TSL:1	n.209+821C>T		intron	N/A
	ENSG00000287369	ENST00000667601.1		n.245C>T		non_coding_transcript_exon	Exon 1 of 1
	IGFBP7-AS1	ENST00000508328.7	TSL:3	n.230+821C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74717 AN: 151880 Hom.: 19278 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.492 AC: 74815 AN: 151998 Hom.: 19314 Cov.: 31 AF XY: 0.496 AC XY: 36848 AN XY: 74298

African (AFR) AF: 0.643 AC: 26644 AN: 41464

American (AMR) AF: 0.387 AC: 5917 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3468

East Asian (EAS) AF: 0.673 AC: 3459 AN: 5142

South Asian (SAS) AF: 0.419 AC: 2021 AN: 4824

European-Finnish (FIN) AF: 0.534 AC: 5639 AN: 10564

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27882 AN: 67944

Other (OTH) AF: 0.467 AC: 988 AN: 2114

Alfa AF: 0.443 Hom.: 20788

Bravo AF: 0.492

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.83
PhyloP100		-0.91
PromoterAI		0.041	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4075349; hg19: chr4-57976957;