chr4-57074860-T-C

Variant names:

• chr4-57074860-T-C
• rs11934877
• NM_001553.3:c.476-33927A>G

Variant summary

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

The NM_001553.3(IGFBP7):​c.476-33927A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,260 control chromosomes in the GnomAD database, including 1,647 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 0.14 (1647 hom., cov: 33)
• Consequence: IGFBP7 NM_001553.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632
• Publications: 7 publications found

Genes affected

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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001553.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP7	NM_001553.3	MANE Select	c.476-33927A>G		intron	N/A	NP_001544.1
	IGFBP7	NM_001253835.2		c.476-33927A>G		intron	N/A	NP_001240764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP7	ENST00000295666.6	TSL:1 MANE Select	c.476-33927A>G		intron	N/A	ENSP00000295666.4
	IGFBP7	ENST00000514062.2	TSL:2	c.476-33927A>G		intron	N/A	ENSP00000486293.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21798 AN: 152142 Hom.: 1645 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0814

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.143 AC: 21815 AN: 152260 Hom.: 1647 Cov.: 33 AF XY: 0.142 AC XY: 10588 AN XY: 74462

African (AFR) AF: 0.141 AC: 5859 AN: 41544

American (AMR) AF: 0.150 AC: 2295 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3466

East Asian (EAS) AF: 0.0812 AC: 422 AN: 5194

South Asian (SAS) AF: 0.143 AC: 691 AN: 4832

European-Finnish (FIN) AF: 0.130 AC: 1377 AN: 10606

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10111 AN: 68010

Other (OTH) AF: 0.143 AC: 302 AN: 2112

Alfa AF: 0.148 Hom.: 5404

Bravo AF: 0.145

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.5
DANN	Benign	0.85
PhyloP100		0.63
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: rs11934877; hg19: chr4-57941026;