rs367949344

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.403G>A(p.Ala135Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000583 in 1,554,400 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 3 hom. )

Consequence

IGFBP7
NM_001553.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.08

Publications

2 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=0.0058704615).

BP6

Variant 4-57109949-C-T is Benign according to our data. Variant chr4-57109949-C-T is described in ClinVar as Benign. ClinVar VariationId is 3045248.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 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.403G>A	p.Ala135Thr	missense	Exon 1 of 5	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2		c.403G>A	p.Ala135Thr	missense	Exon 1 of 4	NP_001240764.1	Q16270-2
IGFBP7-AS1	NR_034081.1		n.188C>T		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGFBP7	ENST00000295666.6	TSL:1 MANE Select	c.403G>A	p.Ala135Thr	missense	Exon 1 of 5	ENSP00000295666.4	Q16270-1
IGFBP7-AS1	ENST00000499667.6	TSL:1	n.188C>T		non_coding_transcript_exon	Exon 1 of 5
IGFBP7	ENST00000896424.1		c.403G>A	p.Ala135Thr	missense	Exon 1 of 7	ENSP00000566483.1

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.00130

AC:

200

AN:

153752

AF XY:

0.00133

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000773

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000398

Gnomad OTH exome

AF:

0.00255

GnomAD4 exome

AF:

0.000585

AC:

820

AN:

1402174

Hom.:

Cov.:

AF XY:

0.000598

AC XY:

415

AN XY:

693600

show subpopulations

African (AFR)

AF:

0.0000308

AC:

AN:

32426

American (AMR)

AF:

0.000240

AC:

AN:

37430

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

508

AN:

25196

East Asian (EAS)

AF:

0.00

AC:

AN:

37242

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37036

Middle Eastern (MID)

AF:

0.00204

AC:

AN:

5388

European-Non Finnish (NFE)

AF:

0.000155

AC:

169

AN:

1088512

Other (OTH)

AF:

0.00207

AC:

121

AN:

58516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000565

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0207

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68034

Other (OTH)

AF:

0.000956

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.00212

Hom.:

Bravo

AF:

0.000608

ESP6500AA

AF:

0.000240

AC:

ESP6500EA

AF:

0.000851

AC:

ExAC

AF:

0.000656

AC:

ClinVar

ClinVar submissions

Significance: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

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.83

M_CAP

Benign

0.024

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.3

PhyloP100

2.1

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.27

REVEL

Benign

0.050

Sift

Benign

0.68

Sift4G

Benign

0.69

Polyphen

0.47

Vest4

0.14

MVP

0.19

MPC

0.52

ClinPred

0.035

GERP RS

3.0

PromoterAI

0.036

Neutral

(source)

Varity_R

0.080

gMVP

0.30

Mutation Taster

=97/3

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