Variant chr1-56867696-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000562.3(C8A):c.165C>A(p.Asp55Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000843 in 1,613,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

C8A
NM_000562.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.273

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010531634).

BP6

Variant 1-56867696-C-A is Benign according to our data. Variant chr1-56867696-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1121148.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C8A	NM_000562.3 linkuse as main transcript	c.165C>A	p.Asp55Glu	missense_variant	2/11	ENST00000361249.4
C8A	XM_017002234.2 linkuse as main transcript	c.165C>A	p.Asp55Glu	missense_variant	2/8
C8A	XM_011542079.3 linkuse as main transcript	c.165C>A	p.Asp55Glu	missense_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C8A	ENST00000361249.4 linkuse as main transcript	c.165C>A	p.Asp55Glu	missense_variant	2/11	1	NM_000562.3	P4

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000139

AC:

AN:

251032

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000856

AC:

125

AN:

1460922

Hom.:

Cov.:

AF XY:

0.0000867

AC XY:

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00348

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.3

DANN

Benign

0.90

DEOGEN2

Benign

0.0074

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.56

M_CAP

Benign

0.0038

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.65

REVEL

Benign

0.023

Sift

Benign

0.53

Sift4G

Benign

0.73

Polyphen

0.065

Vest4

0.23

MutPred

0.42

Gain of ubiquitination at K56 (P = 0.0628);

MVP

0.24

MPC

0.031

ClinPred

0.013

GERP RS

-2.1

Varity_R

0.11

gMVP

0.28

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