Variant 4-57040820-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001553.3(IGFBP7):c.585+4T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,592,102 control chromosomes in the GnomAD database, including 109,621 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9335 hom., cov: 33)

Exomes 𝑓: 0.37 ( 100286 hom. )

Consequence

IGFBP7
NM_001553.3 splice_region, intron

Scores

Splicing: ADA: 0.00004899

Clinical Significance

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

Conservation

PhyloP100: 0.323

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 (HGNC:):

IGFBP7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-57040820-A-T is Benign according to our data. Variant chr4-57040820-A-T is described in ClinVar as [Benign]. Clinvar id is 1299709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-57040820-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGFBP7	NM_001553.3 linkuse as main transcript	c.585+4T>A		splice_region_variant, intron_variant		ENST00000295666.6	NP_001544.1	Q16270-1
IGFBP7	NM_001253835.2 linkuse as main transcript	c.585+4T>A		splice_region_variant, intron_variant			NP_001240764.1	Q16270-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
IGFBP7	ENST00000295666.6 linkuse as main transcript	c.585+4T>A	splice_region_variant, intron_variant	1	NM_001553.3	ENSP00000295666.4	Q16270-1
IGFBP7	ENST00000514062.2 linkuse as main transcript	c.585+4T>A	splice_region_variant, intron_variant	2		ENSP00000486293.1	Q16270-2
IGFBP7	ENST00000512512.3 linkuse as main transcript	n.225+4T>A	splice_region_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.345

AC:

52434

AN:

152040

Hom.:

9325

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.351

GnomAD3 exomes

AF:

0.347

AC:

86887

AN:

250386

Hom.:

15835

AF XY:

0.359

AC XY:

48610

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.317

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.476

Gnomad EAS exome

AF:

0.218

Gnomad SAS exome

AF:

0.419

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.364

GnomAD4 exome

AF:

0.369

AC:

530628

AN:

1439946

Hom.:

100286

Cov.:

AF XY:

0.373

AC XY:

267692

AN XY:

717908

show subpopulations

Gnomad4 AFR exome

AF:

0.305

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.483

Gnomad4 EAS exome

AF:

0.207

Gnomad4 SAS exome

AF:

0.423

Gnomad4 FIN exome

AF:

0.335

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.372

GnomAD4 genome

AF:

0.345

AC:

52482

AN:

152156

Hom.:

9335

Cov.:

AF XY:

0.345

AC XY:

25634

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.311

Gnomad4 AMR

AF:

0.280

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.402

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.380

Gnomad4 OTH

AF:

0.351

Alfa

AF:

0.383

Hom.:

3760

Bravo

AF:

0.337

Asia WGS

AF:

0.292

AC:

1017

AN:

3478

EpiCase

AF:

0.392

EpiControl

AF:

0.397

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial retinal arterial macroaneurysm

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000049

dbscSNV1_RF

Benign

0.012

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