Genetic Variant IGFBP7-AS1:n.209+430C>G (chr4-57110400-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000947223.1(IGFBP7):c.-49G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 1,249,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

IGFBP7
ENST00000947223.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.96

Publications

5 publications found

Variant links:

Genes affected

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

IGFBP7-AS1 links:

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

IGFBP7 links:

ENSG00000287369 (HGNC:):

ENSG00000287369 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000947223.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGFBP7-AS1	NR_034081.1		n.209+430C>G	intron	N/A
IGFBP7	NM_001553.3	MANE Select	c.-49G>C	upstream_gene	N/A	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2		c.-49G>C	upstream_gene	N/A	NP_001240764.1	Q16270-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IGFBP7-AS1	ENST00000499667.6	TSL:1	n.209+430C>G	intron	N/A
IGFBP7	ENST00000947223.1		c.-49G>C	5_prime_UTR	Exon 1 of 6	ENSP00000617282.1
IGFBP7	ENST00000896421.1		c.-49G>C	5_prime_UTR	Exon 1 of 6	ENSP00000566480.1

Frequencies

GnomAD3 genomes

AF:

0.00000661

AC:

AN:

151212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.10e-7

AC:

AN:

1098476

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

524992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22342

American (AMR)

AF:

0.00

AC:

AN:

7874

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13800

East Asian (EAS)

AF:

0.00

AC:

AN:

25066

South Asian (SAS)

AF:

0.00

AC:

AN:

28370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2880

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

931790

Other (OTH)

AF:

0.00

AC:

AN:

43602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73834

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41298

American (AMR)

AF:

0.00

AC:

AN:

15170

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67740

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.45

(source)

DANN

Benign

0.81

PhyloP100

-6.0

PromoterAI

0.074

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over