1-56956811-C-G

Position:

• chr1-56956811-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000066.4(C8B):​c.349G>C​(p.Gly117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 31)
• Consequence: C8B NM_000066.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.950

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058417916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C8B	NM_000066.4	c.349G>C	p.Gly117Arg	missense_variant	3/12	ENST00000371237.9	NP_000057.3
C8B	NM_001278543.2	c.193G>C	p.Gly65Arg	missense_variant	4/13		NP_001265472.2
C8B	NM_001278544.2	c.163G>C	p.Gly55Arg	missense_variant	4/13		NP_001265473.2
C8B	XM_047429957.1	c.349G>C	p.Gly117Arg	missense_variant	3/7		XP_047285913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C8B	ENST00000371237.9	c.349G>C	p.Gly117Arg	missense_variant	3/12	1	NM_000066.4	ENSP00000360281	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.7
DANN	Benign	0.53
DEOGEN2	Benign	0.0014	.;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.048	.;T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	2.9	N;N;N
REVEL	Benign	0.033
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.76	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.081
MutPred		0.32		.;.;Gain of disorder (P = 0.0794);
MVP		0.22
MPC		0.041
ClinPred		0.70	D
GERP RS		-0.17
gMVP		0.38

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: rs1013579; hg19: chr1-57422484;