rs3813948

chr1-207096513-T-C

Variant summary

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

The NM_001017365.3(C4BPB):c.410-9T>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 0.0785 in 1,554,250 control chromosomes in the GnomAD database, including 5,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 965 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4960 hom. )

Consequence

C4BPB
NM_001017365.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005132

Clinical Significance

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

Conservation

PhyloP100: 0.124

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:

Genome browser will be placed here

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 1-207096513-T-C is Benign according to our data. Variant chr1-207096513-T-C is described in ClinVar as [Benign]. Clinvar id is 402448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 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.410-9T>C		splice_polypyrimidine_tract_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.410-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001017365.3	P4	P20851-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15556

AN:

152052

Hom.:

965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.0789

Gnomad AMR

AF:

0.0775

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.0557

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.0705

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.0912

AC:

22869

AN:

250852

Hom.:

1259

AF XY:

0.0928

AC XY:

12580

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.0518

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.160

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.0564

Gnomad NFE exome

AF:

0.0768

Gnomad OTH exome

AF:

0.0985

GnomAD4 exome

AF:

0.0760

AC:

106513

AN:

1402080

Hom.:

4960

Cov.:

AF XY:

0.0778

AC XY:

54586

AN XY:

701354

show subpopulations

Gnomad4 AFR exome

AF:

0.165

Gnomad4 AMR exome

AF:

0.0543

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.0553

Gnomad4 NFE exome

AF:

0.0659

Gnomad4 OTH exome

AF:

0.0911

GnomAD4 genome

AF:

0.102

AC:

15564

AN:

152170

Hom.:

965

Cov.:

AF XY:

0.101

AC XY:

7521

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.0775

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.0557

Gnomad4 NFE

AF:

0.0705

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.0821

Hom.:

1283

Bravo

AF:

0.106

Asia WGS

AF:

0.151

AC:

524

AN:

3478

EpiCase

AF:

0.0808

EpiControl

AF:

0.0824

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

1.5

Dann

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000051

dbscSNV1_RF

Benign

0.0

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