rs2808470

Variant names:

• chr1-207113842-C-T
• rs2808470
• NM_000715.4:c.143-258C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-207113842-C-T
• chr1-207113842-C-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000715.4(C4BPA):​c.143-258C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,854 control chromosomes in the GnomAD database, including 13,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (13569 hom., cov: 31)
• Consequence: C4BPA NM_000715.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55
• Publications: 16 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-207113842-C-T is Benign according to our data. Variant chr1-207113842-C-T is described in ClinVar as Benign. ClinVar VariationId is 1267035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 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.143-258C>T		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.143-258C>T		intron	N/A	ENSP00000356037.3	P04003
	C4BPA	ENST00000902686.1		c.143-147C>T		intron	N/A	ENSP00000572745.1
	C4BPA	ENST00000902687.1		c.143-147C>T		intron	N/A	ENSP00000572746.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52151 AN: 151740 Hom.: 13532 Cov.: 31

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.344 AC: 52240 AN: 151854 Hom.: 13569 Cov.: 31 AF XY: 0.337 AC XY: 25030 AN XY: 74250

African (AFR) AF: 0.732 AC: 30281 AN: 41384

American (AMR) AF: 0.293 AC: 4474 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3468

East Asian (EAS) AF: 0.202 AC: 1041 AN: 5158

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4814

European-Finnish (FIN) AF: 0.120 AC: 1270 AN: 10552

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.177 AC: 12045 AN: 67906

Other (OTH) AF: 0.329 AC: 694 AN: 2108

Alfa AF: 0.217 Hom.: 9473

Bravo AF: 0.372

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.045
DANN	Benign	0.45
PhyloP100		-1.6
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: rs2808470; hg19: chr1-207287187; COSMIC: COSV65536007;