4-57068436-C-T

Variant names:

• chr4-57068436-C-T
• rs1714022
• NM_001553.3:c.476-27503G>A

Variant summary

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

The NM_001553.3(IGFBP7):​c.476-27503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,950 control chromosomes in the GnomAD database, including 24,029 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 0.55 (24029 hom., cov: 32)
• Consequence: IGFBP7 NM_001553.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 4 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.64 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP7	NM_001553.3	MANE Select	c.476-27503G>A		intron	N/A	NP_001544.1	Q16270-1
	IGFBP7	NM_001253835.2		c.476-27503G>A		intron	N/A	NP_001240764.1	Q16270-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP7	ENST00000295666.6	TSL:1 MANE Select	c.476-27503G>A		intron	N/A	ENSP00000295666.4	Q16270-1
	IGFBP7	ENST00000896424.1		c.451-25359G>A		intron	N/A	ENSP00000566483.1
	IGFBP7	ENST00000947223.1		c.476-26514G>A		intron	N/A	ENSP00000617282.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83365 AN: 151832 Hom.: 24023 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.549 AC: 83393 AN: 151950 Hom.: 24029 Cov.: 32 AF XY: 0.550 AC XY: 40797 AN XY: 74234

African (AFR) AF: 0.362 AC: 15007 AN: 41438

American (AMR) AF: 0.651 AC: 9933 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2080 AN: 3468

East Asian (EAS) AF: 0.547 AC: 2825 AN: 5164

South Asian (SAS) AF: 0.586 AC: 2825 AN: 4822

European-Finnish (FIN) AF: 0.592 AC: 6220 AN: 10500

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42713 AN: 67976

Other (OTH) AF: 0.560 AC: 1181 AN: 2110

Alfa AF: 0.604 Hom.: 15676

Bravo AF: 0.543

Asia WGS AF: 0.565 AC: 1963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.69
PhyloP100		-1.0
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: rs1714022; hg19: chr4-57934602;