rs11934877

Positions:

• chr4-57074860-T-C

Variant summary

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

The ENST00000295666.6(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 ENST00000295666.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.632

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP7	NM_001553.3	c.476-33927A>G		intron_variant		ENST00000295666.6	NP_001544.1
IGFBP7	NM_001253835.2	c.476-33927A>G		intron_variant			NP_001240764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP7	ENST00000295666.6	c.476-33927A>G		intron_variant		1	NM_001553.3	ENSP00000295666	P2
IGFBP7	ENST00000514062.2	c.476-33927A>G		intron_variant		2		ENSP00000486293	A2

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

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0812

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.143

Alfa AF: 0.151 Hom.: 2363

Bravo AF: 0.145

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.5
DANN	Benign	0.85

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: rs11934877; hg19: chr4-57941026;