1-207124139-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000715.4(C4BPA):c.515-36G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,584,796 control chromosomes in the GnomAD database, including 147,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (15838 hom., cov: 32)
  • Exomes 𝑓: 0.43 (131782 hom.)
• Consequence: C4BPA NM_000715.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.428

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-207124139-G-C is Benign according to our data. Variant chr1-207124139-G-C is described in ClinVar as [Benign]. Clinvar id is 1276972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C4BPA	NM_000715.4	c.515-36G>C		intron_variant		ENST00000367070.8
C4BPA	XM_005273251.3	c.515-36G>C		intron_variant
C4BPA	XM_005273252.5	c.515-36G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4BPA	ENST00000367070.8	c.515-36G>C		intron_variant		1	NM_000715.4	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68447 AN: 151858 Hom.: 15809 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.456

GnomAD3 exomes AF: 0.454 AC: 112670 AN: 248190 Hom.: 26259 AF XY: 0.450 AC XY: 60438 AN XY: 134280

Gnomad AFR exome AF: 0.517

Gnomad AMR exome AF: 0.529

Gnomad ASJ exome AF: 0.407

Gnomad EAS exome AF: 0.613

Gnomad SAS exome AF: 0.502

Gnomad FIN exome AF: 0.370

Gnomad NFE exome AF: 0.403

Gnomad OTH exome AF: 0.461

GnomAD4 exome AF: 0.426 AC: 610085 AN: 1432820 Hom.: 131782 Cov.: 25 AF XY: 0.428 AC XY: 304842 AN XY: 713056

Gnomad4 AFR exome AF: 0.514

Gnomad4 AMR exome AF: 0.523

Gnomad4 ASJ exome AF: 0.411

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.451 AC: 68529 AN: 151976 Hom.: 15838 Cov.: 32 AF XY: 0.453 AC XY: 33623 AN XY: 74290

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.462

Alfa AF: 0.324 Hom.: 1340

Bravo AF: 0.467

Asia WGS AF: 0.631 AC: 2190 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.93
Cadd	Benign	1.2
Dann	Benign	0.39

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: rs2842707; hg19: chr1-207297484; COSMIC: COSV65535939; COSMIC: COSV65535939;