Genetic Variant IGFBP7:p.Gly124Ser (chr4-57109982-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001553.3(IGFBP7):c.370G>A(p.Gly124Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000945 in 1,545,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

IGFBP7
NM_001553.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.86

Publications

3 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.09283778).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001553.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGFBP7	NM_001553.3	MANE Select	c.370G>A	p.Gly124Ser	missense	Exon 1 of 5	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2		c.370G>A	p.Gly124Ser	missense	Exon 1 of 4	NP_001240764.1	Q16270-2
IGFBP7-AS1	NR_034081.1		n.209+12C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGFBP7	ENST00000295666.6	TSL:1 MANE Select	c.370G>A	p.Gly124Ser	missense	Exon 1 of 5	ENSP00000295666.4	Q16270-1
IGFBP7-AS1	ENST00000499667.6	TSL:1	n.209+12C>T		intron	N/A
IGFBP7	ENST00000896424.1		c.370G>A	p.Gly124Ser	missense	Exon 1 of 7	ENSP00000566483.1

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000140

AC:

AN:

143368

AF XY:

0.0000767

show subpopulations

Gnomad AFR exome

AF:

0.00186

Gnomad AMR exome

AF:

0.000199

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

AF:

0.0000488

AC:

AN:

1393212

Hom.:

Cov.:

AF XY:

0.0000392

AC XY:

AN XY:

688376

show subpopulations

African (AFR)

AF:

0.00143

AC:

AN:

32124

American (AMR)

AF:

0.000164

AC:

AN:

36490

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25142

East Asian (EAS)

AF:

0.00

AC:

AN:

36478

South Asian (SAS)

AF:

0.00

AC:

AN:

79836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5420

European-Non Finnish (NFE)

AF:

0.00000277

AC:

AN:

1083336

Other (OTH)

AF:

0.000224

AC:

AN:

58160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000512

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41572

American (AMR)

AF:

0.000392

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000599

Hom.:

Bravo

AF:

0.000665

ESP6500AA

AF:

0.00167

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000799

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.89

M_CAP

Pathogenic

0.59

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

PhyloP100

6.9

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-4.4

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.48

MVP

0.32

MPC

1.3

ClinPred

0.70

GERP RS

2.4

PromoterAI

0.052

Neutral

(source)

Varity_R

0.77

gMVP

0.66

Mutation Taster

=67/33

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over