NM_001017365.3:c.58+46T>G

Variant names:

• chr1-207089635-T-G
• rs12711513
• NM_001017365.3:c.58+46T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001017365.3(C4BPB):​c.58+46T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,539,668 control chromosomes in the GnomAD database, including 221,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21729 hom., cov: 31)
  • Exomes 𝑓: 0.53 (199302 hom.)
• Consequence: C4BPB NM_001017365.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0320
• Publications: 16 publications found

Genes affected

C4BPB (HGNC:1328): (complement component 4 binding protein beta) This gene encodes a member of a superfamily of proteins composed predominantly of tandemly arrayed short consensus repeats of approximately 60 amino acids. A single, unique beta-chain encoded by this gene assembles with seven identical alpha-chains into the predominant isoform of C4b-binding protein, a multimeric protein that controls activation of the complement cascade through the classical pathway. C4b-binding protein has a regulatory role in the coagulation system also, mediated through the beta-chain binding of protein S, a vitamin K-dependent protein that serves as a cofactor of activated protein C. 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. Alternative splicing gives rise to multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-207089635-T-G is Benign according to our data. Variant chr1-207089635-T-G is described in ClinVar as Benign. ClinVar VariationId is 1274277.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017365.3. 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
	C4BPB	NM_001017365.3	MANE Select	c.58+46T>G		intron	N/A	NP_001017365.1	P20851-1
	C4BPB	NM_000716.3		c.58+46T>G		intron	N/A	NP_000707.1	P20851-1
	C4BPB	NM_001017367.1		c.58+46T>G		intron	N/A	NP_001017367.1	P20851-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4BPB	ENST00000367078.8	TSL:1 MANE Select	c.58+46T>G		intron	N/A	ENSP00000356045.3	P20851-1
	C4BPB	ENST00000243611.9	TSL:1	c.58+46T>G		intron	N/A	ENSP00000243611.5	P20851-1
	C4BPB	ENST00000367076.7	TSL:1	c.58+46T>G		intron	N/A	ENSP00000356043.3	P20851-2

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80108 AN: 151782 Hom.: 21700 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.476

GnomAD2 exomes AF: 0.571 AC: 141472 AN: 247690 AF XY: 0.563

Gnomad AFR exome AF: 0.519

Gnomad AMR exome AF: 0.716

Gnomad ASJ exome AF: 0.436

Gnomad EAS exome AF: 0.847

Gnomad FIN exome AF: 0.546

Gnomad NFE exome AF: 0.497

Gnomad OTH exome AF: 0.526

GnomAD4 exome AF: 0.530 AC: 734888 AN: 1387768 Hom.: 199302 Cov.: 22 AF XY: 0.530 AC XY: 367856 AN XY: 694582

African (AFR) AF: 0.513 AC: 16434 AN: 32026

American (AMR) AF: 0.702 AC: 31267 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 11232 AN: 25634

East Asian (EAS) AF: 0.887 AC: 34934 AN: 39368

South Asian (SAS) AF: 0.611 AC: 51772 AN: 84726

European-Finnish (FIN) AF: 0.539 AC: 28749 AN: 53350

Middle Eastern (MID) AF: 0.379 AC: 2116 AN: 5578

European-Non Finnish (NFE) AF: 0.506 AC: 528517 AN: 1044686

Other (OTH) AF: 0.516 AC: 29867 AN: 57882

GnomAD4 genome AF: 0.528 AC: 80182 AN: 151900 Hom.: 21729 Cov.: 31 AF XY: 0.534 AC XY: 39658 AN XY: 74240

African (AFR) AF: 0.518 AC: 21455 AN: 41382

American (AMR) AF: 0.571 AC: 8706 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1482 AN: 3472

East Asian (EAS) AF: 0.857 AC: 4424 AN: 5162

South Asian (SAS) AF: 0.626 AC: 3016 AN: 4816

European-Finnish (FIN) AF: 0.555 AC: 5855 AN: 10548

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33746 AN: 67950

Other (OTH) AF: 0.474 AC: 998 AN: 2104

Alfa AF: 0.505 Hom.: 31778

Bravo AF: 0.532

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.36
PhyloP100		-0.032
PromoterAI		0.065	Neutral
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: rs12711513; hg19: chr1-207262980;