1-207114485-CT-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000715.4(C4BPA):c.328+226del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (13 hom., cov: 19)
  • Failed GnomAD Quality Control
• Consequence: C4BPA NM_000715.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0460

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 1-207114485-CT-C is Benign according to our data. Variant chr1-207114485-CT-C is described in ClinVar as [Benign]. Clinvar id is 1249174.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C4BPA	NM_000715.4	c.328+226del		intron_variant		ENST00000367070.8
C4BPA	XM_005273251.3	c.328+226del		intron_variant
C4BPA	XM_005273252.5	c.328+226del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4BPA	ENST00000367070.8	c.328+226del		intron_variant		1	NM_000715.4	P1
C4BPA	ENST00000421786.5	c.328+226del		intron_variant		4
C4BPA	ENST00000424088.1	c.329-165del		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3958 AN: 59420 Hom.: 13 Cov.: 19 FAILED QC

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0383

Gnomad AMR AF: 0.0293

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.0837

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.00376

Gnomad MID AF: 0.0300

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0544

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0667 AC: 3961 AN: 59408 Hom.: 13 Cov.: 19 AF XY: 0.0624 AC XY: 1741 AN XY: 27896

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0293

Gnomad4 ASJ AF: 0.0735

Gnomad4 EAS AF: 0.0843

Gnomad4 SAS AF: 0.0396

Gnomad4 FIN AF: 0.00376

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.0544

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs34895847; hg19: chr1-207287830;