Variant 1-56883734-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000562.3(C8A):c.855+53A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,434,640 control chromosomes in the GnomAD database, including 19,666 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2178 hom., cov: 33)

Exomes 𝑓: 0.15 ( 17488 hom. )

Consequence

C8A
NM_000562.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.81

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
C8A	NM_000562.3 link	c.855+53A>T	intron_variant	ENST00000361249.4	NP_000553.1	P07357
C8A	XM_017002234.2 link	c.855+53A>T	intron_variant		XP_016857723.1
C8A	XM_011542079.3 link	c.855+53A>T	intron_variant		XP_011540381.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C8A	ENST00000361249.4 link	c.855+53A>T		intron_variant		1	NM_000562.3	ENSP00000354458.3		P07357

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23797

AN:

152042

Hom.:

2165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.147

GnomAD4 exome

AF:

0.152

AC:

195372

AN:

1282480

Hom.:

17488

AF XY:

0.150

AC XY:

97213

AN XY:

646162

show subpopulations

Gnomad4 AFR exome

AF:

0.120

Gnomad4 AMR exome

AF:

0.354

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.384

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.191

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.157

AC:

23853

AN:

152160

Hom.:

2178

Cov.:

AF XY:

0.165

AC XY:

12244

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.123

Gnomad4 EAS

AF:

0.352

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.202

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.0690

Hom.:

Bravo

AF:

0.162

Asia WGS

AF:

0.241

AC:

838

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.73

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over