Variant 1-207124335-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000715.4(C4BPA):c.675T>C(p.Gly225=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,612,826 control chromosomes in the GnomAD database, including 578,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 56324 hom., cov: 31)

Exomes 𝑓: 0.84 ( 521847 hom. )

Consequence

C4BPA
NM_000715.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.651

Variant links:

Genes affected

C4BPA (HGNC:1325): (complement component 4 binding protein alpha) This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. Along with a single, unique beta-chain, seven identical alpha-chains encoded by this gene assemble into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. 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. Two pseudogenes of this gene are also found in the cluster. [provided by RefSeq, Jul 2008]

C4BPA links:

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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 1-207124335-T-C is Benign according to our data. Variant chr1-207124335-T-C is described in ClinVar as [Benign]. Clinvar id is 402444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-207124335-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.651 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C4BPA	NM_000715.4 linkuse as main transcript	c.675T>C	p.Gly225=	synonymous_variant	6/12	ENST00000367070.8
C4BPA	XM_005273251.3 linkuse as main transcript	c.675T>C	p.Gly225=	synonymous_variant	6/12
C4BPA	XM_005273252.5 linkuse as main transcript	c.675T>C	p.Gly225=	synonymous_variant	6/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4BPA	ENST00000367070.8 linkuse as main transcript	c.675T>C	p.Gly225=	synonymous_variant	6/12	1	NM_000715.4	P1

Frequencies

GnomAD3 genomes

AF:

0.859

AC:

130672

AN:

152038

Hom.:

56266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.904

Gnomad AMI

AF:

0.807

Gnomad AMR

AF:

0.865

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.796

Gnomad SAS

AF:

0.878

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.838

Gnomad OTH

AF:

0.839

GnomAD3 exomes

AF:

0.855

AC:

214046

AN:

250328

Hom.:

91753

AF XY:

0.851

AC XY:

115161

AN XY:

135270

show subpopulations

Gnomad AFR exome

AF:

0.909

Gnomad AMR exome

AF:

0.905

Gnomad ASJ exome

AF:

0.771

Gnomad EAS exome

AF:

0.812

Gnomad SAS exome

AF:

0.876

Gnomad FIN exome

AF:

0.882

Gnomad NFE exome

AF:

0.837

Gnomad OTH exome

AF:

0.835

GnomAD4 exome

AF:

0.845

AC:

1233705

AN:

1460670

Hom.:

521847

Cov.:

AF XY:

0.845

AC XY:

613903

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.904

Gnomad4 AMR exome

AF:

0.902

Gnomad4 ASJ exome

AF:

0.775

Gnomad4 EAS exome

AF:

0.788

Gnomad4 SAS exome

AF:

0.876

Gnomad4 FIN exome

AF:

0.884

Gnomad4 NFE exome

AF:

0.841

Gnomad4 OTH exome

AF:

0.832

GnomAD4 genome

AF:

0.860

AC:

130791

AN:

152156

Hom.:

56324

Cov.:

AF XY:

0.862

AC XY:

64080

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.904

Gnomad4 AMR

AF:

0.865

Gnomad4 ASJ

AF:

0.767

Gnomad4 EAS

AF:

0.796

Gnomad4 SAS

AF:

0.878

Gnomad4 FIN

AF:

0.880

Gnomad4 NFE

AF:

0.838

Gnomad4 OTH

AF:

0.839

Alfa

AF:

0.841

Hom.:

45956

Bravo

AF:

0.860

Asia WGS

AF:

0.812

AC:

2827

AN:

3478

EpiCase

AF:

0.826

EpiControl

AF:

0.826

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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

DANN

Benign

0.41

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