Variant chr1-56867639-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000562.3(C8A):c.108A>G(p.Ala36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0176 in 1,613,766 control chromosomes in the GnomAD database, including 295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 15 hom., cov: 32)

Exomes 𝑓: 0.018 ( 280 hom. )

Consequence

C8A
NM_000562.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.05

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-56867639-A-G is Benign according to our data. Variant chr1-56867639-A-G is described in ClinVar as [Benign]. Clinvar id is 1168914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0123 (1872/152306) while in subpopulation NFE AF= 0.0205 (1398/68032). AF 95% confidence interval is 0.0197. There are 15 homozygotes in gnomad4. There are 812 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
C8A	NM_000562.3 linkuse as main transcript	c.108A>G	p.Ala36=	synonymous_variant	2/11	ENST00000361249.4
C8A	XM_017002234.2 linkuse as main transcript	c.108A>G	p.Ala36=	synonymous_variant	2/8
C8A	XM_011542079.3 linkuse as main transcript	c.108A>G	p.Ala36=	synonymous_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C8A	ENST00000361249.4 linkuse as main transcript	c.108A>G	p.Ala36=	synonymous_variant	2/11	1	NM_000562.3	P4

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1872

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0106

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.00527

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0205

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0128

AC:

3223

AN:

251052

Hom.:

AF XY:

0.0131

AC XY:

1772

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.00768

Gnomad ASJ exome

AF:

0.0139

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00536

Gnomad FIN exome

AF:

0.00573

Gnomad NFE exome

AF:

0.0209

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0181

AC:

26510

AN:

1461460

Hom.:

280

Cov.:

AF XY:

0.0174

AC XY:

12681

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.00323

Gnomad4 AMR exome

AF:

0.00819

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00546

Gnomad4 FIN exome

AF:

0.00652

Gnomad4 NFE exome

AF:

0.0212

Gnomad4 OTH exome

AF:

0.0193

GnomAD4 genome

AF:

0.0123

AC:

1872

AN:

152306

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

812

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00327

Gnomad4 AMR

AF:

0.0106

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.00527

Gnomad4 NFE

AF:

0.0205

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0170

Hom.:

Bravo

AF:

0.0123

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0202

EpiControl

AF:

0.0176

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.58

DANN

Benign

0.48

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