Variant chr1-207089635-T-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.58+46T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,539,668 control chromosomes in the GnomAD database, including 221,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21729 hom., cov: 31)

Exomes 𝑓: 0.53 ( 199302 hom. )

Consequence

C4BPB
NM_001017365.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0320

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=-0.83).

BP6

Variant 1-207089635-T-G is Benign according to our data. Variant chr1-207089635-T-G is described in ClinVar as [Benign]. Clinvar id is 1274277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 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.58+46T>G		intron_variant		ENST00000367078.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4BPB	ENST00000367078.8 linkuse as main transcript	c.58+46T>G		intron_variant		1	NM_001017365.3	P4	P20851-1

Frequencies

GnomAD3 genomes

AF:

0.528

AC:

80108

AN:

151782

Hom.:

21700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.555

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.497

Gnomad OTH

AF:

0.476

GnomAD3 exomes

AF:

0.571

AC:

141472

AN:

247690

Hom.:

42238

AF XY:

0.563

AC XY:

75464

AN XY:

134060

show subpopulations

Gnomad AFR exome

AF:

0.519

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.436

Gnomad EAS exome

AF:

0.847

Gnomad SAS exome

AF:

0.610

Gnomad FIN exome

AF:

0.546

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.526

GnomAD4 exome

AF:

0.530

AC:

734888

AN:

1387768

Hom.:

199302

Cov.:

AF XY:

0.530

AC XY:

367856

AN XY:

694582

show subpopulations

Gnomad4 AFR exome

AF:

0.513

Gnomad4 AMR exome

AF:

0.702

Gnomad4 ASJ exome

AF:

0.438

Gnomad4 EAS exome

AF:

0.887

Gnomad4 SAS exome

AF:

0.611

Gnomad4 FIN exome

AF:

0.539

Gnomad4 NFE exome

AF:

0.506

Gnomad4 OTH exome

AF:

0.516

GnomAD4 genome

AF:

0.528

AC:

80182

AN:

151900

Hom.:

21729

Cov.:

AF XY:

0.534

AC XY:

39658

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.518

Gnomad4 AMR

AF:

0.571

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.857

Gnomad4 SAS

AF:

0.626

Gnomad4 FIN

AF:

0.555

Gnomad4 NFE

AF:

0.497

Gnomad4 OTH

AF:

0.474

Alfa

AF:

0.494

Hom.:

19452

Bravo

AF:

0.532

Asia WGS

AF:

0.726

AC:

2524

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	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.7

DANN

Benign

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