rs2842704

Positions:

• chr1-207116091-G-A
• chr1-207116091-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000715.4(C4BPA):​c.428+576G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,186 control chromosomes in the GnomAD database, including 51,436 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51436 hom., cov: 32)
• Consequence: C4BPA NM_000715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C4BPA	NM_000715.4	c.428+576G>A		intron_variant		ENST00000367070.8
C4BPA	XM_005273251.3	c.428+576G>A		intron_variant
C4BPA	XM_005273252.5	c.428+576G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4BPA	ENST00000367070.8	c.428+576G>A		intron_variant		1	NM_000715.4	P1
C4BPA	ENST00000421786.5	c.428+576G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124812 AN: 152068 Hom.: 51399 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.865

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.817

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.821 AC: 124905 AN: 152186 Hom.: 51436 Cov.: 32 AF XY: 0.822 AC XY: 61136 AN XY: 74398

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.852

Gnomad4 OTH AF: 0.819

Alfa AF: 0.838 Hom.: 70094

Bravo AF: 0.817

Asia WGS AF: 0.777 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.33
DANN	Benign	0.37

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: rs2842704; hg19: chr1-207289436;