rs4074555

chr4-57110400-C-Achr4-57110400-C-Gchr4-57110400-C-T

Variant summary

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

The NR_034081.1(IGFBP7-AS1):n.209+430C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,249,564 control chromosomes in the GnomAD database, including 9,567 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 0.15 (2500 hom., cov: 32)
  • Exomes 𝑓: 0.096 (7067 hom.)
• Consequence: IGFBP7-AS1 NR_034081.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.96

Genes affected

IGFBP7-AS1 (HGNC:40296): (IGFBP7 antisense RNA 1)

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGFBP7-AS1	NR_034081.1	n.209+430C>A		intron_variant, non_coding_transcript_variant
IGFBP7	NM_001553.3			upstream_gene_variant		ENST00000295666.6
IGFBP7	NM_001253835.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGFBP7-AS1	ENST00000499667.6	n.209+430C>A		intron_variant, non_coding_transcript_variant		1
IGFBP7-AS1	ENST00000508328.6	n.191+430C>A		intron_variant, non_coding_transcript_variant		3
IGFBP7	ENST00000295666.6			upstream_gene_variant		1	NM_001553.3	P2
IGFBP7	ENST00000514062.2			upstream_gene_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23200 AN: 151194 Hom.: 2501 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0707

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.0797

Gnomad OTH AF: 0.136

GnomAD3 exomes AF: 0.374 AC: 119 AN: 318 Hom.: 22 AF XY: 0.342 AC XY: 69 AN XY: 202

Gnomad AFR exome AF: 0.674

Gnomad AMR exome AF: 0.438

Gnomad ASJ exome AF: 0.500

Gnomad EAS exome AF: 0.500

Gnomad SAS exome AF: 0.321

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.500

GnomAD4 exome AF: 0.0956 AC: 105000 AN: 1098262 Hom.: 7067 Cov.: 31 AF XY: 0.0959 AC XY: 50335 AN XY: 524888

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.392

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.0718

Gnomad4 NFE exome AF: 0.0807

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.154 AC: 23226 AN: 151302 Hom.: 2500 Cov.: 32 AF XY: 0.154 AC XY: 11360 AN XY: 73942

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0707

Gnomad4 NFE AF: 0.0797

Gnomad4 OTH AF: 0.135

Alfa AF: 0.0345 Hom.: 34

Bravo AF: 0.168

Asia WGS AF: 0.198 AC: 657 AN: 3324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.38
Dann	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4074555; hg19: chr4-57976566;