Variant 4-57110102-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000295666.6(IGFBP7):c.250G>A(p.Gly84Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000217 in 1,382,286 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

IGFBP7
ENST00000295666.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.03

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IGFBP7	NM_001553.3 linkuse as main transcript	c.250G>A	p.Gly84Ser	missense_variant	1/5	ENST00000295666.6	NP_001544.1
IGFBP7-AS1	NR_034081.1 linkuse as main transcript	n.209+132C>T		intron_variant, non_coding_transcript_variant
IGFBP7	NM_001253835.2 linkuse as main transcript	c.250G>A	p.Gly84Ser	missense_variant	1/4		NP_001240764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP7	ENST00000295666.6 linkuse as main transcript	c.250G>A	p.Gly84Ser	missense_variant	1/5	1	NM_001553.3	ENSP00000295666	P2	Q16270-1
IGFBP7-AS1	ENST00000499667.6 linkuse as main transcript	n.209+132C>T		intron_variant, non_coding_transcript_variant		1
IGFBP7-AS1	ENST00000508328.6 linkuse as main transcript	n.191+132C>T		intron_variant, non_coding_transcript_variant		3
IGFBP7	ENST00000514062.2 linkuse as main transcript	c.250G>A	p.Gly84Ser	missense_variant	1/4	2		ENSP00000486293	A2	Q16270-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1382286

Hom.:

Cov.:

AF XY:

0.00000439

AC XY:

AN XY:

683076

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:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2022

The c.250G>A (p.G84S) alteration is located in exon 1 (coding exon 1) of the IGFBP7 gene. This alteration results from a G to A substitution at nucleotide position 250, causing the glycine (G) at amino acid position 84 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.

Eigen

Uncertain

0.31

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.83

T;T

M_CAP

Pathogenic

0.79

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-2.6

D;.

REVEL

Uncertain

0.31

Sift

Uncertain

0.0060

D;.

Sift4G

Uncertain

0.013

D;D

Polyphen

0.94

P;.

Vest4

0.28

MutPred

0.32

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.60

MPC

1.3

ClinPred

0.99

GERP RS

3.5

Varity_R

0.83

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over