C8B p.Arg274Arg

Variant names:

• chr1-56949596-C-C
• NM_000066.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-56949597--
• chr1-56949597-T-A
• chr1-56949597-T-G
• chr1-56949597-T-C
• chr1-56949599-G-T
• chr1-56949597-TCG-CCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000066.4(C8B):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C8B NM_000066.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 0 publications found

Genes affected

C8B (HGNC:1353): (complement C8 beta chain) This gene encodes one of the three subunits of the complement component 8 (C8) protein. C8 is composed of equimolar amounts of alpha, beta and gamma subunits, which are encoded by three separate genes. C8 is one component of the membrane attack complex, which mediates cell lysis, and it initiates membrane penetration of the complex. This protein mediates the interaction of C8 with the C5b-7 membrane attack complex precursor. In humans deficiency of this protein is associated with increased risk of meningococcal infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

C8B Gene-Disease associations (from GenCC):

• type II complement component 8 deficiency

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000066.4. 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
	C8B	NM_000066.4	MANE Select	c.		exon_region	Exon 6 of 12	NP_000057.3	P07358
	C8B	NM_001278543.2		c.		exon_region	Exon 7 of 13	NP_001265472.2
	C8B	NM_001278544.2		c.		exon_region	Exon 7 of 13	NP_001265473.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C8B	ENST00000371237.9	TSL:1 MANE Select	c.		exon_region	Exon 6 of 12	ENSP00000360281.4	P07358
	C8B	ENST00000696164.1		c.		exon_region	Exon 7 of 13	ENSP00000512454.1	A0A8Q3WL56
	C8B	ENST00000875298.1		c.		exon_region	Exon 7 of 13	ENSP00000545357.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.25

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-57415269;