rs11573018

Variant names:

• chr4-57110554-C-T
• rs11573018
• ENST00000499667.6:n.209+584C>T

Variant summary

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

The ENST00000947223.1(IGFBP7):​c.-203G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,640 control chromosomes in the GnomAD database, including 1,209 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 0.12 (1209 hom., cov: 32)
• Consequence: IGFBP7 ENST00000947223.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 3 publications found

Genes affected

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

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

ENSG00000287369 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000947223.1. 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+584C>T		intron	N/A
	IGFBP7	NM_001553.3	MANE Select	c.-203G>A		upstream_gene	N/A	NP_001544.1	Q16270-1
	IGFBP7	NM_001253835.2		c.-203G>A		upstream_gene	N/A	NP_001240764.1	Q16270-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP7-AS1	ENST00000499667.6	TSL:1	n.209+584C>T		intron	N/A
	IGFBP7	ENST00000947223.1		c.-203G>A		5_prime_UTR	Exon 1 of 6	ENSP00000617282.1
	IGFBP7	ENST00000896421.1		c.-203G>A		5_prime_UTR	Exon 1 of 6	ENSP00000566480.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18004 AN: 151528 Hom.: 1209 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.00234

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.119 AC: 18005 AN: 151640 Hom.: 1209 Cov.: 32 AF XY: 0.121 AC XY: 8955 AN XY: 74098

African (AFR) AF: 0.0763 AC: 3166 AN: 41484

American (AMR) AF: 0.0969 AC: 1478 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 467 AN: 3462

East Asian (EAS) AF: 0.00234 AC: 12 AN: 5122

South Asian (SAS) AF: 0.0608 AC: 293 AN: 4822

European-Finnish (FIN) AF: 0.214 AC: 2238 AN: 10442

Middle Eastern (MID) AF: 0.182 AC: 53 AN: 292

European-Non Finnish (NFE) AF: 0.147 AC: 9944 AN: 67756

Other (OTH) AF: 0.122 AC: 257 AN: 2102

Alfa AF: 0.136 Hom.: 190

Bravo AF: 0.109

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.62
DANN	Benign	0.95
PhyloP100		-2.3
PromoterAI		-0.35	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11573018; hg19: chr4-57976720;