dbSNP rs548051457: IGFBP7:p.Gly144Val (chr4-57109921-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001553.3(IGFBP7):c.431G>T(p.Gly144Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,405,176 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.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

IGFBP7
NM_001553.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.63

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2508243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP7	NM_001553.3 link	c.431G>T	p.Gly144Val	missense_variant	Exon 1 of 5	ENST00000295666.6	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2 link	c.431G>T	p.Gly144Val	missense_variant	Exon 1 of 4		NP_001240764.1	Q16270-2
IGFBP7-AS1	NR_034081.1 link	n.160C>A		non_coding_transcript_exon_variant	Exon 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGFBP7	ENST00000295666.6 link	c.431G>T	p.Gly144Val	missense_variant	Exon 1 of 5	1	NM_001553.3	ENSP00000295666.4	Q16270-1
IGFBP7-AS1	ENST00000499667.6 link	n.160C>A		non_coding_transcript_exon_variant	Exon 1 of 5	1
IGFBP7	ENST00000514062.2 link	c.431G>T	p.Gly144Val	missense_variant	Exon 1 of 4	2		ENSP00000486293.1	Q16270-2
IGFBP7-AS1	ENST00000508328.6 link	n.142C>A		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.12e-7

AC:

AN:

1405176

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695562

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000267

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

-0.024

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.1

M;M

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.6

D;.

REVEL

Benign

0.15

Sift

Uncertain

0.028

D;.

Sift4G

Benign

0.075

T;T

Polyphen

1.0

D;.

Vest4

0.62

MutPred

0.42

Gain of glycosylation at S142 (P = 0.0085);Gain of glycosylation at S142 (P = 0.0085);

MVP

0.42

MPC

1.4

ClinPred

0.96

GERP RS

2.0

Varity_R

0.22

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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