Variant 4-57032562-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000295666.6(IGFBP7):c.703-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00615 in 1,602,276 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 44 hom. )

Consequence

IGFBP7
ENST00000295666.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001463

Clinical Significance

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

Conservation

PhyloP100: 0.108

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 4-57032562-A-G is Benign according to our data. Variant chr4-57032562-A-G is described in ClinVar as [Benign]. Clinvar id is 782942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP7	NM_001553.3 linkuse as main transcript	c.703-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000295666.6	NP_001544.1
IGFBP7	NM_001253835.2 linkuse as main transcript	c.703-10T>C		splice_polypyrimidine_tract_variant, intron_variant			NP_001240764.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
IGFBP7	ENST00000295666.6 linkuse as main transcript	c.703-10T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_001553.3	ENSP00000295666	P2	Q16270-1
IGFBP7	ENST00000514062.2 linkuse as main transcript	c.703-10T>C	splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000486293	A2	Q16270-2
IGFBP7	ENST00000512512.3 linkuse as main transcript	n.343-10T>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.00432

AC:

657

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00414

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00752

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00386

AC:

969

AN:

251260

Hom.:

AF XY:

0.00388

AC XY:

527

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00421

Gnomad NFE exome

AF:

0.00702

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00634

AC:

9198

AN:

1449934

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

4461

AN XY:

722268

show subpopulations

Gnomad4 AFR exome

AF:

0.000632

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.000499

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00470

Gnomad4 NFE exome

AF:

0.00777

Gnomad4 OTH exome

AF:

0.00484

GnomAD4 genome

AF:

0.00431

AC:

657

AN:

152342

Hom.:

Cov.:

AF XY:

0.00379

AC XY:

282

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00414

Gnomad4 NFE

AF:

0.00753

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00571

Hom.:

Bravo

AF:

0.00410

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

-0.77

CADD

Benign

8.4

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0080

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