Variant 4-57040848-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000295666.6(IGFBP7):c.561G>A(p.Pro187=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,613,072 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 5 hom., cov: 33)

Exomes 𝑓: 0.011 ( 120 hom. )

Consequence

IGFBP7
ENST00000295666.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.105

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 4-57040848-C-T is Benign according to our data. Variant chr4-57040848-C-T is described in ClinVar as [Benign]. Clinvar id is 791477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.105 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP7	NM_001553.3 linkuse as main transcript	c.561G>A	p.Pro187=	synonymous_variant	2/5	ENST00000295666.6	NP_001544.1
IGFBP7	NM_001253835.2 linkuse as main transcript	c.561G>A	p.Pro187=	synonymous_variant	2/4		NP_001240764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGFBP7	ENST00000295666.6 linkuse as main transcript	c.561G>A	p.Pro187=	synonymous_variant	2/5	1	NM_001553.3	ENSP00000295666	P2	Q16270-1
IGFBP7	ENST00000514062.2 linkuse as main transcript	c.561G>A	p.Pro187=	synonymous_variant	2/4	2		ENSP00000486293	A2	Q16270-2
IGFBP7	ENST00000512512.3 linkuse as main transcript	n.201G>A		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.00735

AC:

1118

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00857

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00758

AC:

1904

AN:

251220

Hom.:

AF XY:

0.00768

AC XY:

1043

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00983

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00412

Gnomad FIN exome

AF:

0.00993

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.0106

AC:

15459

AN:

1460754

Hom.:

120

Cov.:

AF XY:

0.0104

AC XY:

7533

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.00182

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.00895

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00459

Gnomad4 FIN exome

AF:

0.0104

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.00830

GnomAD4 genome

AF:

0.00733

AC:

1117

AN:

152318

Hom.:

Cov.:

AF XY:

0.00729

AC XY:

543

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.00857

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.0106

Hom.:

Bravo

AF:

0.00672

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0108

EpiControl

AF:

0.0107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

7.2

DANN

Benign

0.63

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

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