rs11120218

Positions:

• chr1-207105106-G-A

Variant summary

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

The NM_000715.4(C4BPA):​c.-26+676G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,090 control chromosomes in the GnomAD database, including 5,115 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 0.22 (5115 hom., cov: 32)
• Consequence: C4BPA NM_000715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C4BPA	NM_000715.4	c.-26+676G>A		intron_variant		ENST00000367070.8	NP_000706.1
C4BPA	XM_005273251.3	c.-29+676G>A		intron_variant			XP_005273308.1
C4BPA	XM_005273252.5	c.-128+676G>A		intron_variant			XP_005273309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C4BPA	ENST00000367070.8	c.-26+676G>A		intron_variant		1	NM_000715.4	ENSP00000356037	P1
C4BPA	ENST00000421786.5	c.-128+676G>A		intron_variant		4		ENSP00000403386
C4BPA	ENST00000424088.1	c.-26+676G>A		intron_variant, NMD_transcript_variant		4		ENSP00000395968

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33683 AN: 151972 Hom.: 5106 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.222 AC: 33718 AN: 152090 Hom.: 5115 Cov.: 32 AF XY: 0.217 AC XY: 16113 AN XY: 74332

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.231

Alfa AF: 0.157 Hom.: 3036

Bravo AF: 0.237

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.62

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: rs11120218; hg19: chr1-207278451;