4-57110097-C-T

Variant summary

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

The ENST00000295666.6(IGFBP7):​c.255G>A​(p.Met85Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IGFBP7
ENST00000295666.6 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47
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-AS1 (HGNC:40296): (IGFBP7 antisense RNA 1)

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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=0.21479559).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGFBP7NM_001553.3 linkuse as main transcriptc.255G>A p.Met85Ile missense_variant 1/5 ENST00000295666.6 NP_001544.1
IGFBP7-AS1NR_034081.1 linkuse as main transcriptn.209+127C>T intron_variant, non_coding_transcript_variant
IGFBP7NM_001253835.2 linkuse as main transcriptc.255G>A p.Met85Ile missense_variant 1/4 NP_001240764.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGFBP7ENST00000295666.6 linkuse as main transcriptc.255G>A p.Met85Ile missense_variant 1/51 NM_001553.3 ENSP00000295666 P2Q16270-1
IGFBP7-AS1ENST00000499667.6 linkuse as main transcriptn.209+127C>T intron_variant, non_coding_transcript_variant 1
IGFBP7-AS1ENST00000508328.6 linkuse as main transcriptn.191+127C>T intron_variant, non_coding_transcript_variant 3
IGFBP7ENST00000514062.2 linkuse as main transcriptc.255G>A p.Met85Ile missense_variant 1/42 ENSP00000486293 A2Q16270-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1385554
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
684860
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsAug 13, 2021The c.255G>A (p.M85I) 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 255, causing the methionine (M) at amino acid position 85 to be replaced by an isoleucine (I). 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
Pathogenic
0.90
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.027
T;.
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.33
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.84
T;T
M_CAP
Uncertain
0.27
D
MetaRNN
Benign
0.21
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.3
M;M
MutationTaster
Benign
0.91
D;D
PrimateAI
Pathogenic
0.96
D
PROVEAN
Benign
-0.69
N;.
REVEL
Benign
0.075
Sift
Uncertain
0.022
D;.
Sift4G
Uncertain
0.042
D;D
Polyphen
0.0
B;.
Vest4
0.36
MutPred
0.23
Gain of glycosylation at Y80 (P = 0.0322);Gain of glycosylation at Y80 (P = 0.0322);
MVP
0.32
MPC
0.49
ClinPred
0.74
D
GERP RS
2.2
Varity_R
0.62
gMVP
0.40

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.

Other links and lift over

hg19: chr4-57976263; API