1-207096574-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001017365.3(C4BPB):c.462C>T(p.Asn154Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,600,706 control chromosomes in the GnomAD database, including 49,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 15180 hom., cov: 32)

Exomes 𝑓: 0.19 ( 34709 hom. )

Consequence

C4BPB
NM_001017365.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.376

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-207096574-C-T is Benign according to our data. Variant chr1-207096574-C-T is described in ClinVar as [Benign]. Clinvar id is 402449.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207096574-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.376 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C4BPB	NM_001017365.3 link	c.462C>T	p.Asn154Asn	synonymous_variant	Exon 5 of 7	ENST00000367078.8	NP_001017365.1	P20851-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C4BPB	ENST00000367078.8 link	c.462C>T	p.Asn154Asn	synonymous_variant	Exon 5 of 7	1	NM_001017365.3	ENSP00000356045.3		P20851-1

Frequencies

GnomAD3 genomes

AF:

0.356

AC:

54112

AN:

151998

Hom.:

15136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.782

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.271

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.343

GnomAD3 exomes

AF:

0.231

AC:

57747

AN:

249976

Hom.:

9741

AF XY:

0.224

AC XY:

30247

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.795

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.276

Gnomad EAS exome

AF:

0.162

Gnomad SAS exome

AF:

0.256

Gnomad FIN exome

AF:

0.114

Gnomad NFE exome

AF:

0.179

Gnomad OTH exome

AF:

0.221

GnomAD4 exome

AF:

0.190

AC:

275887

AN:

1448590

Hom.:

34709

Cov.:

AF XY:

0.192

AC XY:

138208

AN XY:

721386

show subpopulations

Gnomad4 AFR exome

AF:

0.809

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.180

Gnomad4 SAS exome

AF:

0.252

Gnomad4 FIN exome

AF:

0.117

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.356

AC:

54212

AN:

152116

Hom.:

15180

Cov.:

AF XY:

0.348

AC XY:

25919

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.782

Gnomad4 AMR

AF:

0.297

Gnomad4 ASJ

AF:

0.271

Gnomad4 EAS

AF:

0.165

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.116

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.340

Alfa

AF:

0.264

Hom.:

6776

Bravo

AF:

0.387

Asia WGS

AF:

0.238

AC:

827

AN:

3478

EpiCase

AF:

0.197

EpiControl

AF:

0.192

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-0.88

CADD

Benign

1.2

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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