NM_001553.3:c.167C>G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001553.3(IGFBP7):c.167C>G(p.Ala56Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,390,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A56V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

IGFBP7
NM_001553.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0640

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10228479).

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.167C>G	p.Ala56Gly	missense	Exon 1 of 5	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2		c.167C>G	p.Ala56Gly	missense	Exon 1 of 4	NP_001240764.1	Q16270-2
IGFBP7-AS1	NR_034081.1		n.209+215G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGFBP7	ENST00000295666.6	TSL:1 MANE Select	c.167C>G	p.Ala56Gly	missense	Exon 1 of 5	ENSP00000295666.4	Q16270-1
IGFBP7-AS1	ENST00000499667.6	TSL:1	n.209+215G>C		intron	N/A
IGFBP7	ENST00000896424.1		c.167C>G	p.Ala56Gly	missense	Exon 1 of 7	ENSP00000566483.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

17366

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

AF:

0.00000161

AC:

AN:

1238524

Hom.:

Cov.:

AF XY:

0.00000330

AC XY:

AN XY:

605204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24610

American (AMR)

AF:

0.00

AC:

AN:

13116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17872

East Asian (EAS)

AF:

0.00

AC:

AN:

27658

South Asian (SAS)

AF:

0.0000178

AC:

AN:

56128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30458

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1013850

Other (OTH)

AF:

0.0000196

AC:

AN:

51120

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

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:

0.00000659

AC:

AN:

151844

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67922

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.089

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.093

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.72

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.28

PhyloP100

-0.064

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.2

REVEL

Benign

0.073

Sift

Benign

0.40

Sift4G

Benign

0.49

Polyphen

0.98

Vest4

0.13

MutPred

0.19

Gain of glycosylation at T53 (P = 0.0969)

MVP

0.16

MPC

0.95

ClinPred

0.72

GERP RS

3.5

PromoterAI

0.042

Neutral

(source)

Varity_R

0.20

gMVP

0.35

Mutation Taster

=87/13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over