rs143523574

Variant names:

Variant summary

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

The NM_000562.3(C8A):c.100C>T(p.Pro34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0044 in 1,613,714 control chromosomes in the GnomAD database, including 455 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 54 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 401 hom. )

Consequence

C8A
NM_000562.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.138

Variant links:

Genes affected

C8A (HGNC:1352): (complement C8 alpha chain) C8 is a component of the complement system and contains three polypeptides, alpha, beta and gamma. This gene encodes the alpha subunit of C8. C8 participates in the formation of the membrane attack complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause complement C8 alpha-gamma deficiency. [provided by RefSeq, Nov 2008]

C8A 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=0.0022082627).

BP6

Variant 1-56867631-C-T is Benign according to our data. Variant chr1-56867631-C-T is described in ClinVar as [Benign]. Clinvar id is 1169492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8A	NM_000562.3 link	c.100C>T	p.Pro34Ser	missense_variant	Exon 2 of 11	ENST00000361249.4	NP_000553.1	P07357
C8A	XM_017002234.2 link	c.100C>T	p.Pro34Ser	missense_variant	Exon 2 of 8		XP_016857723.1
C8A	XM_011542079.3 link	c.100C>T	p.Pro34Ser	missense_variant	Exon 2 of 8		XP_011540381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8A	ENST00000361249.4 link	c.100C>T	p.Pro34Ser	missense_variant	Exon 2 of 11	1	NM_000562.3	ENSP00000354458.3		P07357

Frequencies

GnomAD3 genomes

AF:

0.00774

AC:

1178

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0667

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0177

AC:

4440

AN:

251000

Hom.:

302

AF XY:

0.0130

AC XY:

1759

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000564

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.00405

AC:

5921

AN:

1461434

Hom.:

401

Cov.:

AF XY:

0.00336

AC XY:

2441

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.000272

Gnomad4 OTH exome

AF:

0.00349

GnomAD4 genome

AF:

0.00776

AC:

1181

AN:

152280

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

589

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00248

Gnomad4 AMR

AF:

0.0668

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00133

Hom.:

Bravo

AF:

0.0139

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.0133

AC:

1617

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000711

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

- -

C8A-related disorder

Benign:1

May 09, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.3

DANN

Benign

0.93

DEOGEN2

Benign

0.072

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.25

Sift

Benign

0.069

Sift4G

Benign

0.064

Polyphen

0.59

Vest4

0.21

MPC

0.033

ClinPred

0.039

GERP RS

1.1

Varity_R

0.060

gMVP

0.51

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

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