chr4-57073697-T-G

Position:

• chr4-57073697-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000295666.6(IGFBP7):​c.476-32764A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,094 control chromosomes in the GnomAD database, including 2,391 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 0.17 (2391 hom., cov: 31)
• Consequence: IGFBP7 ENST00000295666.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP7	NM_001553.3	c.476-32764A>C		intron_variant		ENST00000295666.6	NP_001544.1
IGFBP7	NM_001253835.2	c.476-32764A>C		intron_variant			NP_001240764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP7	ENST00000295666.6	c.476-32764A>C		intron_variant		1	NM_001553.3	ENSP00000295666	P2
IGFBP7	ENST00000514062.2	c.476-32764A>C		intron_variant		2		ENSP00000486293	A2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26264 AN: 151976 Hom.: 2388 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.173 AC: 26278 AN: 152094 Hom.: 2391 Cov.: 31 AF XY: 0.175 AC XY: 13036 AN XY: 74358

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.166

Alfa AF: 0.130 Hom.: 348

Bravo AF: 0.164

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs10049992; hg19: chr4-57939863;