4-57110251-G-T

Position:

chr4-57110251-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000295666.6(IGFBP7):c.101C>A(p.Pro34His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,399,708 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 5 hom. )

Consequence

IGFBP7
ENST00000295666.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008255869).

BP6

Variant 4-57110251-G-T is Benign according to our data. Variant chr4-57110251-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3045023.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IGFBP7	NM_001553.3 linkuse as main transcript	c.101C>A	p.Pro34His	missense_variant	1/5	ENST00000295666.6	NP_001544.1
IGFBP7-AS1	NR_034081.1 linkuse as main transcript	n.209+281G>T		intron_variant, non_coding_transcript_variant
IGFBP7	NM_001253835.2 linkuse as main transcript	c.101C>A	p.Pro34His	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.101C>A	p.Pro34His	missense_variant	1/5	1	NM_001553.3	ENSP00000295666	P2	Q16270-1
IGFBP7-AS1	ENST00000499667.6 linkuse as main transcript	n.209+281G>T		intron_variant, non_coding_transcript_variant		1
IGFBP7-AS1	ENST00000508328.6 linkuse as main transcript	n.191+281G>T		intron_variant, non_coding_transcript_variant		3
IGFBP7	ENST00000514062.2 linkuse as main transcript	c.101C>A	p.Pro34His	missense_variant	1/4	2		ENSP00000486293	A2	Q16270-2

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00110

AC:

AN:

51976

Hom.:

AF XY:

0.00148

AC XY:

AN XY:

30416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00477

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000275

AC:

343

AN:

1247976

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

249

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:

0.00533

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000593

Gnomad4 OTH exome

AF:

0.000314

GnomAD4 genome

AF:

0.000105

AC:

AN:

151732

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.000820

AC:

Asia WGS

AF:

0.000896

AC:

AN:

3364

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IGFBP7-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 28, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.088

T;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0083

T;T

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

0.67

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.2

D;.

REVEL

Benign

0.24

Sift

Benign

0.083

T;.

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.84

P;.

Vest4

0.41

MutPred

0.26

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

MVP

0.70

MPC

0.49

ClinPred

0.20

GERP RS

1.9

Varity_R

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over