1-207115552-T-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.428+37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,090,848 control chromosomes in the GnomAD database, including 181,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19534 hom., cov: 31)
  • Exomes 𝑓: 0.58 (162068 hom.)
• Consequence: C4BPA NM_000715.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.418

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=-0.83).
• BP6: Variant 1-207115552-T-C is Benign according to our data. Variant chr1-207115552-T-C is described in ClinVar as [Benign]. Clinvar id is 1288103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C4BPA	NM_000715.4	c.428+37T>C		intron_variant		ENST00000367070.8
C4BPA	XM_005273251.3	c.428+37T>C		intron_variant
C4BPA	XM_005273252.5	c.428+37T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4BPA	ENST00000367070.8	c.428+37T>C		intron_variant		1	NM_000715.4	P1
C4BPA	ENST00000421786.5	c.428+37T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74452 AN: 151880 Hom.: 19533 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.490

GnomAD3 exomes AF: 0.569 AC: 94038 AN: 165346 Hom.: 26812 AF XY: 0.570 AC XY: 52749 AN XY: 92556

Gnomad AFR exome AF: 0.322

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.627

Gnomad SAS exome AF: 0.508

Gnomad FIN exome AF: 0.580

Gnomad NFE exome AF: 0.604

Gnomad OTH exome AF: 0.582

GnomAD4 exome AF: 0.582 AC: 546380 AN: 938850 Hom.: 162068 Cov.: 12 AF XY: 0.580 AC XY: 280065 AN XY: 483052

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.555

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.579

Gnomad4 SAS exome AF: 0.508

Gnomad4 FIN exome AF: 0.584

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.490 AC: 74464 AN: 151998 Hom.: 19534 Cov.: 31 AF XY: 0.492 AC XY: 36564 AN XY: 74294

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.488

Alfa AF: 0.515 Hom.: 4766

Bravo AF: 0.480

Asia WGS AF: 0.506 AC: 1755 AN: 3472

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	-0.83
Cadd	Benign	6.4
Dann	Benign	0.58

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: rs12031629; hg19: chr1-207288897; COSMIC: COSV65535955; COSMIC: COSV65535955;