rs1013579

Variant names:

• chr1-56956811-C-T
• rs1013579
• NM_000066.4:c.349G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-56956811-C-T
• chr1-56956811-C-A
• chr1-56956811-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.950
• Publications: 32 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 1169777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

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.349G>A	p.Gly117Arg	missense	Exon 3 of 12	NP_000057.3	P07358
	C8B	NM_001278543.2		c.193G>A	p.Gly65Arg	missense	Exon 4 of 13	NP_001265472.2
	C8B	NM_001278544.2		c.163G>A	p.Gly55Arg	missense	Exon 4 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.349G>A	p.Gly117Arg	missense	Exon 3 of 12	ENSP00000360281.4	P07358
	C8B	ENST00000696164.1		c.349G>A	p.Gly117Arg	missense	Exon 4 of 13	ENSP00000512454.1	A0A8Q3WL56
	C8B	ENST00000875298.1		c.349G>A	p.Gly117Arg	missense	Exon 4 of 13	ENSP00000545357.1

Frequencies

GnomAD3 genomes AF: 0.979 AC: 148906 AN: 152126 Hom.: 72908 Cov.: 31

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

GnomAD2 exomes AF: 0.977 AC: 245666 AN: 251372 AF XY: 0.977

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 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.: 50 AF XY: 0.973 AC XY: 707467 AN XY: 727216

African (AFR) AF: 0.995 AC: 33307 AN: 33476

American (AMR) AF: 0.974 AC: 43579 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.972 AC: 25411 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39698 AN: 39700

South Asian (SAS) AF: 0.988 AC: 85250 AN: 86258

European-Finnish (FIN) AF: 0.980 AC: 52376 AN: 53418

Middle Eastern (MID) AF: 0.969 AC: 5587 AN: 5768

European-Non Finnish (NFE) AF: 0.969 AC: 1077885 AN: 1111928

Other (OTH) AF: 0.974 AC: 58804 AN: 60396

GnomAD4 genome AF: 0.979 AC: 149024 AN: 152244 Hom.: 72967 Cov.: 31 AF XY: 0.980 AC XY: 72926 AN XY: 74418

African (AFR) AF: 0.994 AC: 41318 AN: 41548

American (AMR) AF: 0.973 AC: 14868 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3369 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5137 AN: 5140

South Asian (SAS) AF: 0.989 AC: 4769 AN: 4822

European-Finnish (FIN) AF: 0.985 AC: 10456 AN: 10618

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.968 AC: 65861 AN: 68042

Other (OTH) AF: 0.973 AC: 2055 AN: 2112

Alfa AF: 0.970 Hom.: 240993

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Type II complement component 8 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.042
BayesDel_addAF	Benign	-0.60	T
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	N
LIST_S2	Benign	0.048	T
MetaRNN	Benign	5.8e-7	T
MetaSVM	Benign	-0.95	T
PhyloP100		0.95
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	2.9	N
REVEL	Benign	0.036
Sift	Benign	1.0	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.081
MutPred		0.32		Gain of disorder (P = 0.0794)
MPC		0.041
ClinPred		0.0050	T
GERP RS		-0.17
gMVP		0.38
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1013579; hg19: chr1-57422484; COSMIC: COSV107468577; COSMIC: COSV107468577;