1-207090194-C-T

Position:

• chr1-207090194-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001017365.3(C4BPB):​c.59-114C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 818,044 control chromosomes in the GnomAD database, including 4,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (2971 hom., cov: 32)
  • Exomes 𝑓: 0.030 (1829 hom.)
• Consequence: C4BPB NM_001017365.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.95

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-207090194-C-T is Benign according to our data. Variant chr1-207090194-C-T is described in ClinVar as [Benign]. Clinvar id is 1286738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C4BPB	NM_001017365.3	c.59-114C>T		intron_variant		ENST00000367078.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4BPB	ENST00000367078.8	c.59-114C>T		intron_variant		1	NM_001017365.3	P4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18462 AN: 152000 Hom.: 2969 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.0986

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00382

Gnomad OTH AF: 0.0876

GnomAD4 exome AF: 0.0299 AC: 19885 AN: 665926 Hom.: 1829 AF XY: 0.0304 AC XY: 10377 AN XY: 341674

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.0272

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.0770

Gnomad4 FIN exome AF: 0.0167

Gnomad4 NFE exome AF: 0.00338

Gnomad4 OTH exome AF: 0.0480

GnomAD4 genome AF: 0.122 AC: 18499 AN: 152118 Hom.: 2971 Cov.: 32 AF XY: 0.121 AC XY: 9016 AN XY: 74376

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0305

Gnomad4 EAS AF: 0.0991

Gnomad4 SAS AF: 0.0808

Gnomad4 FIN AF: 0.0257

Gnomad4 NFE AF: 0.00382

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0629 Hom.: 555

Bravo AF: 0.138

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.11
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs11120184; hg19: chr1-207263539;