chr4-57110251-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001553.3(IGFBP7):c.101C>A(p.Pro34His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,399,708 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 5 hom. )

Consequence

IGFBP7
NM_001553.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.284

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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008255869).

BP6

Variant 4-57110251-G-T is Benign according to our data. Variant chr4-57110251-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3045023.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

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.101C>A	p.Pro34His	missense	Exon 1 of 5	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2		c.101C>A	p.Pro34His	missense	Exon 1 of 4	NP_001240764.1	Q16270-2
IGFBP7-AS1	NR_034081.1		n.209+281G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGFBP7	ENST00000295666.6	TSL:1 MANE Select	c.101C>A	p.Pro34His	missense	Exon 1 of 5	ENSP00000295666.4	Q16270-1
IGFBP7-AS1	ENST00000499667.6	TSL:1	n.209+281G>T		intron	N/A
IGFBP7	ENST00000896424.1		c.101C>A	p.Pro34His	missense	Exon 1 of 7	ENSP00000566483.1

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151624

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:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00110

AC:

AN:

51976

AF XY:

0.00148

show subpopulations

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:

0.0000527

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000275

AC:

343

AN:

1247976

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

249

AN XY:

612702

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25414

American (AMR)

AF:

0.00

AC:

AN:

19844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19992

East Asian (EAS)

AF:

0.00

AC:

AN:

27120

South Asian (SAS)

AF:

0.00533

AC:

319

AN:

59884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29972

Middle Eastern (MID)

AF:

0.000555

AC:

AN:

3602

European-Non Finnish (NFE)

AF:

0.00000593

AC:

AN:

1011200

Other (OTH)

AF:

0.000314

AC:

AN:

50948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000105

AC:

AN:

151732

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41498

American (AMR)

AF:

0.00

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00332

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67828

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000820

AC:

Asia WGS

AF:

0.000896

AC:

AN:

3364

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

IGFBP7-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.088

Eigen

Benign

0.17

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.0

PhyloP100

0.28

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.24

Sift

Benign

0.083

Sift4G

Pathogenic

0.0010

Polyphen

0.84

Vest4

0.41

MutPred

0.26

Gain of glycosylation at S29 (P = 0.0405)

MVP

0.70

MPC

0.49

ClinPred

0.20

GERP RS

1.9

PromoterAI

-0.024

Neutral

(source)

Varity_R

0.39

gMVP

0.36

Mutation Taster

=94/6

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