Variant 1-207090484-A-G 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_001017365.3(C4BPB):c.232+3A>G variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,597,846 control chromosomes in the GnomAD database, including 201,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 14676 hom., cov: 32)

Exomes 𝑓: 0.50 ( 186821 hom. )

Consequence

C4BPB
NM_001017365.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.0008636

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.506

Variant links:

Genes affected

C4BPB (HGNC:1328): (complement component 4 binding protein beta) This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. A single, unique beta-chain encoded by this gene assembles with seven identical alpha-chains into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. C4b-binding protein has a regulatory role in the coagulation system also, mediated through the beta-chain binding of protein S, a vitamin K-dependent protein that serves as a cofactor of activated protein C. The genes encoding both alpha and beta chains are located adjacent to each other on human chromosome 1 in the regulator of complement activation gene cluster. Alternative splicing gives rise to multiple transcript variants. [provided by RefSeq, Jul 2008]

C4BPB 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=-0.76).

BP6

Variant 1-207090484-A-G is Benign according to our data. Variant chr1-207090484-A-G is described in ClinVar as [Benign]. Clinvar id is 402446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C4BPB	NM_001017365.3 linkuse as main transcript	c.232+3A>G		splice_donor_region_variant, intron_variant		ENST00000367078.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4BPB	ENST00000367078.8 linkuse as main transcript	c.232+3A>G		splice_donor_region_variant, intron_variant		1	NM_001017365.3	P4	P20851-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60776

AN:

151910

Hom.:

14675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.427

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.759

Gnomad SAS

AF:

0.545

Gnomad FIN

AF:

0.530

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.493

Gnomad OTH

AF:

0.381

GnomAD3 exomes

AF:

0.512

AC:

122102

AN:

238584

Hom.:

33531

AF XY:

0.512

AC XY:

66217

AN XY:

129280

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.617

Gnomad ASJ exome

AF:

0.414

Gnomad EAS exome

AF:

0.772

Gnomad SAS exome

AF:

0.535

Gnomad FIN exome

AF:

0.527

Gnomad NFE exome

AF:

0.495

Gnomad OTH exome

AF:

0.494

GnomAD4 exome

AF:

0.501

AC:

724115

AN:

1445818

Hom.:

186821

Cov.:

AF XY:

0.501

AC XY:

360444

AN XY:

719254

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.600

Gnomad4 ASJ exome

AF:

0.412

Gnomad4 EAS exome

AF:

0.766

Gnomad4 SAS exome

AF:

0.534

Gnomad4 FIN exome

AF:

0.522

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.467

GnomAD4 genome

AF:

0.400

AC:

60783

AN:

152028

Hom.:

14676

Cov.:

AF XY:

0.407

AC XY:

30212

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.130

Gnomad4 AMR

AF:

0.465

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.759

Gnomad4 SAS

AF:

0.546

Gnomad4 FIN

AF:

0.530

Gnomad4 NFE

AF:

0.493

Gnomad4 OTH

AF:

0.381

Alfa

AF:

0.466

Hom.:

40372

Bravo

AF:

0.387

Asia WGS

AF:

0.613

AC:

2127

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	GeneDx	Nov 10, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.7

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00086

dbscSNV1_RF

Benign

0.16

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