Variant rs1754533 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000562.3(C8A):c.1503T>C(p.Pro501=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.062 in 1,614,104 control chromosomes in the GnomAD database, including 4,777 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1254 hom., cov: 33)

Exomes 𝑓: 0.058 ( 3523 hom. )

Consequence

C8A
NM_000562.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.701

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=-0.57).

BP6

Variant 1-56912525-T-C is Benign according to our data. Variant chr1-56912525-T-C is described in ClinVar as [Benign]. Clinvar id is 402463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.701 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C8A	NM_000562.3 linkuse as main transcript	c.1503T>C	p.Pro501=	synonymous_variant	10/11	ENST00000361249.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C8A	ENST00000361249.4 linkuse as main transcript	c.1503T>C	p.Pro501=	synonymous_variant	10/11	1	NM_000562.3	P4

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15593

AN:

152164

Hom.:

1252

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.0415

Gnomad EAS

AF:

0.0520

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.0470

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0457

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.0756

AC:

19000

AN:

251452

Hom.:

1073

AF XY:

0.0752

AC XY:

10218

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.0917

Gnomad ASJ exome

AF:

0.0454

Gnomad EAS exome

AF:

0.0518

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.0484

Gnomad NFE exome

AF:

0.0455

Gnomad OTH exome

AF:

0.0709

GnomAD4 exome

AF:

0.0578

AC:

84518

AN:

1461820

Hom.:

3523

Cov.:

AF XY:

0.0596

AC XY:

43313

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.0927

Gnomad4 ASJ exome

AF:

0.0430

Gnomad4 EAS exome

AF:

0.0650

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.0459

Gnomad4 NFE exome

AF:

0.0454

Gnomad4 OTH exome

AF:

0.0678

GnomAD4 genome

AF:

0.103

AC:

15615

AN:

152284

Hom.:

1254

Cov.:

AF XY:

0.102

AC XY:

7605

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.0415

Gnomad4 EAS

AF:

0.0520

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.0470

Gnomad4 NFE

AF:

0.0457

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0666

Hom.:

282

Bravo

AF:

0.110

Asia WGS

AF:

0.107

AC:

374

AN:

3478

EpiCase

AF:

0.0479

EpiControl

AF:

0.0510

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.4

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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