6-32029581-G-GCT

Variant summary

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

The NM_001002029.4(C4B):c.3694_3695dup(p.Val1233GlnfsTer75) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0042 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0077 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C4B NM_001002029.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53

Genes affected

C4B (HGNC:1324): (complement C4B (Chido/Rodgers blood group)) This gene encodes the basic form of complement factor 4, and together with the C4A gene, is part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 6-32029581-G-GCT is Benign according to our data. Variant chr6-32029581-G-GCT is described in ClinVar as [Benign]. Clinvar id is 2656436.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C4B	NM_001002029.4	c.3694_3695dup	p.Val1233GlnfsTer75	frameshift_variant	29/41	ENST00000435363.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C4B	ENST00000435363.7	c.3694_3695dup	p.Val1233GlnfsTer75	frameshift_variant	29/41	1	NM_001002029.4	P1
C4B	ENST00000425700.3	c.3694_3695dup	p.Val1233GlnfsTer75	frameshift_variant	29/40	1
C4B	ENST00000647698.1	c.2400_2401dup	p.Val802GlnfsTer75	frameshift_variant	19/31
C4B	ENST00000648821.1	n.2307_2308dup		non_coding_transcript_exon_variant	16/27

Frequencies

GnomAD3 genomes AF: 0.00 AC: 617 AN: 146762 Hom.: 0 Cov.: 26 FAILED QC

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.0142

Gnomad AMR AF: 0.000669

Gnomad ASJ AF: 0.000875

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00907

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00692

Gnomad OTH AF: 0.00200

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00769 AC: 11017 AN: 1433524 Hom.: 0 Cov.: 34 AF XY: 0.00737 AC XY: 5256 AN XY: 713360

Gnomad4 AFR exome AF: 0.000901

Gnomad4 AMR exome AF: 0.000809

Gnomad4 ASJ exome AF: 0.000500

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.0149

Gnomad4 NFE exome AF: 0.00906

Gnomad4 OTH exome AF: 0.00487

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00420 AC: 617 AN: 146882 Hom.: 0 Cov.: 26 AF XY: 0.00446 AC XY: 319 AN XY: 71558

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.000668

Gnomad4 ASJ AF: 0.000875

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00907

Gnomad4 NFE AF: 0.00692

Gnomad4 OTH AF: 0.00198

Alfa AF: 0.00632 Hom.: 0

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

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

C4B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs367709216; hg19: chr6-31997358;