rs12057769

Variant names:

• chr1-207106136-G-A
• rs12057769
• NM_000715.4:c.-26+1706G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000715.4(C4BPA):​c.-26+1706G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,082 control chromosomes in the GnomAD database, including 1,000 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 0.10 (1000 hom., cov: 31)
• Consequence: C4BPA NM_000715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C4BPA	NM_000715.4	c.-26+1706G>A		intron_variant	Intron 1 of 11	ENST00000367070.8	NP_000706.1
C4BPA	XM_005273251.3	c.-29+1706G>A		intron_variant	Intron 1 of 11		XP_005273308.1
C4BPA	XM_005273252.5	c.-128+1706G>A		intron_variant	Intron 1 of 11		XP_005273309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C4BPA	ENST00000367070.8	c.-26+1706G>A		intron_variant	Intron 1 of 11	1	NM_000715.4	ENSP00000356037.3
C4BPA	ENST00000421786.5	c.-128+1706G>A		intron_variant	Intron 1 of 4	4		ENSP00000403386.1
C4BPA	ENST00000424088.1	n.-26+1706G>A		intron_variant	Intron 1 of 4	4		ENSP00000395968.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15768 AN: 151964 Hom.: 1000 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0783

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0601

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0698

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.104 AC: 15777 AN: 152082 Hom.: 1000 Cov.: 31 AF XY: 0.103 AC XY: 7671 AN XY: 74342

African (AFR) AF: 0.163 AC: 6740 AN: 41470

American (AMR) AF: 0.0783 AC: 1197 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.201 AC: 1039 AN: 5168

South Asian (SAS) AF: 0.129 AC: 623 AN: 4812

European-Finnish (FIN) AF: 0.0601 AC: 636 AN: 10588

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.0698 AC: 4742 AN: 67968

Other (OTH) AF: 0.119 AC: 251 AN: 2110

Alfa AF: 0.117 Hom.: 286

Bravo AF: 0.107

Asia WGS AF: 0.180 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.081
DANN	Benign	0.31
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12057769; hg19: chr1-207279481;