rs11120218

Variant names:

• chr1-207105106-G-A
• rs11120218
• NM_000715.4:c.-26+676G>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+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
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4BPA	NM_000715.4	MANE Select	c.-26+676G>A		intron	N/A	NP_000706.1	P04003

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4BPA	ENST00000367070.8	TSL:1 MANE Select	c.-26+676G>A		intron	N/A	ENSP00000356037.3	P04003
	C4BPA	ENST00000902686.1		c.-26+676G>A		intron	N/A	ENSP00000572745.1
	C4BPA	ENST00000902687.1		c.-128+676G>A		intron	N/A	ENSP00000572746.1

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

African (AFR) AF: 0.433 AC: 17960 AN: 41448

American (AMR) AF: 0.167 AC: 2549 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1040 AN: 5170

South Asian (SAS) AF: 0.159 AC: 767 AN: 4822

European-Finnish (FIN) AF: 0.101 AC: 1069 AN: 10594

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8879 AN: 67990

Other (OTH) AF: 0.231 AC: 488 AN: 2110

Alfa AF: 0.164 Hom.: 4339

Bravo AF: 0.237

Asia WGS AF: 0.212 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.62
PhyloP100		-1.8
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: rs11120218; hg19: chr1-207278451;