dbSNP rs570122247: IGFBP7:p.Pro34Leu (chr4-57110251-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001553.3(IGFBP7):c.101C>T(p.Pro34Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000801 in 1,247,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P34H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

IGFBP7
NM_001553.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.284

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36851034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP7	NM_001553.3 link	c.101C>T	p.Pro34Leu	missense_variant	Exon 1 of 5	ENST00000295666.6	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2 link	c.101C>T	p.Pro34Leu	missense_variant	Exon 1 of 4		NP_001240764.1	Q16270-2
IGFBP7-AS1	NR_034081.1 link	n.209+281G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGFBP7	ENST00000295666.6 link	c.101C>T	p.Pro34Leu	missense_variant	Exon 1 of 5	1	NM_001553.3	ENSP00000295666.4	Q16270-1
IGFBP7-AS1	ENST00000499667.6 link	n.209+281G>A		intron_variant	Intron 1 of 4	1
IGFBP7	ENST00000514062.2 link	c.101C>T	p.Pro34Leu	missense_variant	Exon 1 of 4	2		ENSP00000486293.1	Q16270-2
IGFBP7-AS1	ENST00000508328.6 link	n.191+281G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.01e-7

AC:

AN:

1247978

Hom.:

Cov.:

AF XY:

0.00000163

AC XY:

AN XY:

612702

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.89e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.7

M;M

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-4.2

D;.

REVEL

Benign

0.15

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.0

B;.

Vest4

0.22

MutPred

0.25

Gain of glycosylation at S29 (P = 0.0405);Gain of glycosylation at S29 (P = 0.0405);

MVP

0.65

MPC

0.43

ClinPred

0.98

GERP RS

1.9

Varity_R

0.40

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over