dbSNP rs11573018: IGFBP7-AS1:n.209+584C>T (chr4-57110554-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000499667.6(IGFBP7-AS1):n.209+584C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,640 control chromosomes in the GnomAD database, including 1,209 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 0.12 ( 1209 hom., cov: 32)

Consequence

IGFBP7-AS1
ENST00000499667.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

Publications

3 publications found

Variant links:

Genes affected

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

IGFBP7-AS1 links:

ENSG00000287369 (HGNC:):

ENSG00000287369 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet

IGFBP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IGFBP7-AS1	NR_034081.1 link	n.209+584C>T	intron_variant	Intron 1 of 4
IGFBP7	NM_001553.3 link	c.-203G>A	upstream_gene_variant		ENST00000295666.6	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2 link	c.-203G>A	upstream_gene_variant			NP_001240764.1	Q16270-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP7	ENST00000295666.6 link	c.-203G>A		upstream_gene_variant		1	NM_001553.3	ENSP00000295666.4		Q16270-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18004

AN:

151528

Hom.:

1209

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0765

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0969

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.00234

Gnomad SAS

AF:

0.0605

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.178

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.124

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

GnomAD4 genome

AF:

0.119

AC:

18005

AN:

151640

Hom.:

1209

Cov.:

AF XY:

0.121

AC XY:

8955

AN XY:

74098

show subpopulations

African (AFR)

AF:

0.0763

AC:

3166

AN:

41484

American (AMR)

AF:

0.0969

AC:

1478

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

467

AN:

3462

East Asian (EAS)

AF:

0.00234

AC:

AN:

5122

South Asian (SAS)

AF:

0.0608

AC:

293

AN:

4822

European-Finnish (FIN)

AF:

0.214

AC:

2238

AN:

10442

Middle Eastern (MID)

AF:

0.182

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.147

AC:

9944

AN:

67756

Other (OTH)

AF:

0.122

AC:

257

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

786

1572

2357

3143

3929

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.136

Hom.:

190

Bravo

AF:

0.109

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.62

(source)

DANN

Benign

0.95

PhyloP100

-2.3

PromoterAI

-0.35

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

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