4-57068436-C-T

Position:

• chr4-57068436-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP7	NM_001553.3	c.476-27503G>A		intron_variant		ENST00000295666.6
IGFBP7	NM_001253835.2	c.476-27503G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP7	ENST00000295666.6	c.476-27503G>A		intron_variant		1	NM_001553.3	P2
IGFBP7	ENST00000514062.2	c.476-27503G>A		intron_variant		2		A2

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

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.560

Alfa AF: 0.606 Hom.: 14147

Bravo AF: 0.543

Asia WGS AF: 0.565 AC: 1963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.37
DANN	Benign	0.69

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: rs1714022; hg19: chr4-57934602;