1-56956811-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000066.4(C8B):c.349G>A(p.Gly117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.973 in 1,614,046 control chromosomes in the GnomAD database, including 764,602 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G117E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.98 ( 72967 hom., cov: 31)

Exomes 𝑓: 0.97 ( 691635 hom. )

Consequence

C8B
NM_000066.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.950

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.8007174E-7).

BP6

Variant 1-56956811-C-T is Benign according to our data. Variant chr1-56956811-C-T is described in ClinVar as [Benign]. Clinvar id is 1169777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-56956811-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8B	NM_000066.4 link	c.349G>A	p.Gly117Arg	missense_variant	Exon 3 of 12	ENST00000371237.9	NP_000057.3	P07358
C8B	NM_001278543.2 link	c.193G>A	p.Gly65Arg	missense_variant	Exon 4 of 13		NP_001265472.2	B7Z555
C8B	NM_001278544.2 link	c.163G>A	p.Gly55Arg	missense_variant	Exon 4 of 13		NP_001265473.2	B7Z550
C8B	XM_047429957.1 link	c.349G>A	p.Gly117Arg	missense_variant	Exon 3 of 7		XP_047285913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8B	ENST00000371237.9 link	c.349G>A	p.Gly117Arg	missense_variant	Exon 3 of 12	1	NM_000066.4	ENSP00000360281.4		P07358

Frequencies

GnomAD3 genomes

AF:

0.979

AC:

148906

AN:

152126

Hom.:

72908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.994

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

0.973

Gnomad ASJ

AF:

0.970

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.989

Gnomad FIN

AF:

0.985

Gnomad MID

AF:

0.959

Gnomad NFE

AF:

0.968

Gnomad OTH

AF:

0.973

GnomAD3 exomes

AF:

0.977

AC:

245666

AN:

251372

Hom.:

120098

AF XY:

0.977

AC XY:

132678

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.994

Gnomad AMR exome

AF:

0.975

Gnomad ASJ exome

AF:

0.974

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.990

Gnomad FIN exome

AF:

0.982

Gnomad NFE exome

AF:

0.968

Gnomad OTH exome

AF:

0.967

GnomAD4 exome

AF:

0.973

AC:

1421897

AN:

1461802

Hom.:

691635

Cov.:

AF XY:

0.973

AC XY:

707467

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.995

Gnomad4 AMR exome

AF:

0.974

Gnomad4 ASJ exome

AF:

0.972

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.988

Gnomad4 FIN exome

AF:

0.980

Gnomad4 NFE exome

AF:

0.969

Gnomad4 OTH exome

AF:

0.974

GnomAD4 genome

AF:

0.979

AC:

149024

AN:

152244

Hom.:

72967

Cov.:

AF XY:

0.980

AC XY:

72926

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.994

Gnomad4 AMR

AF:

0.973

Gnomad4 ASJ

AF:

0.970

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.989

Gnomad4 FIN

AF:

0.985

Gnomad4 NFE

AF:

0.968

Gnomad4 OTH

AF:

0.973

Alfa

AF:

0.969

Hom.:

174819

Bravo

AF:

0.978

TwinsUK

AF:

0.970

AC:

3596

ALSPAC

AF:

0.977

AC:

3765

ESP6500AA

AF:

0.993

AC:

4373

ESP6500EA

AF:

0.967

AC:

8318

ExAC

AF:

0.977

AC:

118661

Asia WGS

AF:

0.995

AC:

3462

AN:

3478

EpiCase

AF:

0.965

EpiControl

AF:

0.966

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Type II complement component 8 deficiency

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.8

DANN

Benign

0.53

DEOGEN2

Benign

0.0014

.;T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.048

.;T;T

MetaRNN

Benign

5.8e-7

T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Uncertain

0.49

PROVEAN

Benign

2.9

N;N;N

REVEL

Benign

0.036

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);

MPC

0.041

ClinPred

0.0050

GERP RS

-0.17

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over