Genetic Variant IGFBP7:p.Arg78Gly (chr4-57110120-T-C) – 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 NM_001553.3(IGFBP7):c.232A>G(p.Arg78Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R78K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IGFBP7
NM_001553.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.422

Publications

12 publications found

Variant links:

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]

IGFBP7 links:

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

IGFBP7-AS1 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 (MetaRNN=0.05428633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP7	NM_001553.3 link	c.232A>G	p.Arg78Gly	missense_variant	Exon 1 of 5	ENST00000295666.6	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2 link	c.232A>G	p.Arg78Gly	missense_variant	Exon 1 of 4		NP_001240764.1	Q16270-2
IGFBP7-AS1	NR_034081.1 link	n.209+150T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP7	ENST00000295666.6 link	c.232A>G	p.Arg78Gly	missense_variant	Exon 1 of 5	1	NM_001553.3	ENSP00000295666.4		Q16270-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

104692

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1360504

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

671432

African (AFR)

AF:

0.00

AC:

AN:

27988

American (AMR)

AF:

0.00

AC:

AN:

33418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24192

East Asian (EAS)

AF:

0.00

AC:

AN:

32262

South Asian (SAS)

AF:

0.00

AC:

AN:

76532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5056

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069420

Other (OTH)

AF:

0.00

AC:

AN:

56778

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000111

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.44

T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.1

N;N

PhyloP100

0.42

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.4

N;.

REVEL

Benign

0.034

Sift

Benign

0.29

T;.

Sift4G

Benign

0.44

T;T

Polyphen

0.012

B;.

Vest4

0.25

MutPred

0.30

Loss of methylation at R78 (P = 0.0126);Loss of methylation at R78 (P = 0.0126);

MVP

0.067

MPC

0.55

ClinPred

0.18

GERP RS

0.94

PromoterAI

0.019

Neutral

(source)

Varity_R

0.18

gMVP

0.46

Mutation Taster

=85/15

polymorphism

(source)

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

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over