Variant 1-56867638-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000562.3(C8A):c.107C>A(p.Ala36Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0137 in 1,613,714 control chromosomes in the GnomAD database, including 732 homozygotes. In-silico tool predicts 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. A36V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0089 ( 52 hom., cov: 32)

Exomes 𝑓: 0.014 ( 680 hom. )

Consequence

C8A
NM_000562.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.35

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=0.0024751425).

BP6

Variant 1-56867638-C-A is Benign according to our data. Variant chr1-56867638-C-A is described in ClinVar as [Benign]. Clinvar id is 1164179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C8A	NM_000562.3 linkuse as main transcript	c.107C>A	p.Ala36Glu	missense_variant	2/11	ENST00000361249.4
C8A	XM_017002234.2 linkuse as main transcript	c.107C>A	p.Ala36Glu	missense_variant	2/8
C8A	XM_011542079.3 linkuse as main transcript	c.107C>A	p.Ala36Glu	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C8A	ENST00000361249.4 linkuse as main transcript	c.107C>A	p.Ala36Glu	missense_variant	2/11	1	NM_000562.3	P4

Frequencies

GnomAD3 genomes

AF:

0.00890

AC:

1354

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00836

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.0196

AC:

4928

AN:

251026

Hom.:

238

AF XY:

0.0252

AC XY:

3414

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00368

Gnomad ASJ exome

AF:

0.0167

Gnomad EAS exome

AF:

0.00174

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.00374

Gnomad NFE exome

AF:

0.00795

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0142

AC:

20753

AN:

1461414

Hom.:

680

Cov.:

AF XY:

0.0174

AC XY:

12666

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.00360

Gnomad4 ASJ exome

AF:

0.0162

Gnomad4 EAS exome

AF:

0.000807

Gnomad4 SAS exome

AF:

0.111

Gnomad4 FIN exome

AF:

0.00358

Gnomad4 NFE exome

AF:

0.00836

Gnomad4 OTH exome

AF:

0.0150

GnomAD4 genome

AF:

0.00889

AC:

1354

AN:

152300

Hom.:

Cov.:

AF XY:

0.00999

AC XY:

744

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.0147

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00836

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00809

Hom.:

Bravo

AF:

0.00552

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00860

AC:

ExAC

AF:

0.0215

AC:

2608

Asia WGS

AF:

0.0680

AC:

234

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Type I complement component 8 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.059

Eigen

Benign

0.15

Eigen_PC

Benign

0.036

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0025

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.68

REVEL

Uncertain

0.39

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.22

MPC

0.19

ClinPred

0.033

GERP RS

5.1

Varity_R

0.24

gMVP

0.44

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