rs2230214

Variant names:

Variant summary

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

The NM_001735.3(C5):c.1461C>T(p.Thr487Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,607,578 control chromosomes in the GnomAD database, including 9,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 914 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8160 hom. )

Consequence

C5
NM_001735.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0620

Variant links:

Genes affected

C5 (HGNC:1331): (complement C5) This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge. Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

C5 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=-0.64).

BP6

Variant 9-121020021-G-A is Benign according to our data. Variant chr9-121020021-G-A is described in ClinVar as [Benign]. Clinvar id is 402456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.062 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001735.3 link	c.1461C>T	p.Thr487Thr	synonymous_variant	Exon 12 of 41	ENST00000223642.3	NP_001726.2	P01031
C5	NM_001317163.2 link	c.1479C>T	p.Thr493Thr	synonymous_variant	Exon 12 of 41		NP_001304092.1	P01031A0A8Q3SID6Q59GS8
C5	NM_001317164.2 link	c.1461C>T	p.Thr487Thr	synonymous_variant	Exon 12 of 21		NP_001304093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3 link	c.1461C>T	p.Thr487Thr	synonymous_variant	Exon 12 of 41	1	NM_001735.3	ENSP00000223642.1		P01031

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16117

AN:

151954

Hom.:

914

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0781

Gnomad ASJ

AF:

0.0591

Gnomad EAS

AF:

0.0325

Gnomad SAS

AF:

0.0911

Gnomad FIN

AF:

0.0624

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.0823

GnomAD3 exomes

AF:

0.0905

AC:

22746

AN:

251272

Hom.:

1240

AF XY:

0.0897

AC XY:

12176

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.0682

Gnomad ASJ exome

AF:

0.0650

Gnomad EAS exome

AF:

0.0354

Gnomad SAS exome

AF:

0.0809

Gnomad FIN exome

AF:

0.0607

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.0854

GnomAD4 exome

AF:

0.101

AC:

147033

AN:

1455506

Hom.:

8160

Cov.:

AF XY:

0.100

AC XY:

72639

AN XY:

724524

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.0687

Gnomad4 ASJ exome

AF:

0.0617

Gnomad4 EAS exome

AF:

0.0286

Gnomad4 SAS exome

AF:

0.0804

Gnomad4 FIN exome

AF:

0.0648

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.0961

GnomAD4 genome

AF:

0.106

AC:

16121

AN:

152072

Hom.:

914

Cov.:

AF XY:

0.104

AC XY:

7701

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.141

Gnomad4 AMR

AF:

0.0778

Gnomad4 ASJ

AF:

0.0591

Gnomad4 EAS

AF:

0.0322

Gnomad4 SAS

AF:

0.0912

Gnomad4 FIN

AF:

0.0624

Gnomad4 NFE

AF:

0.109

Gnomad4 OTH

AF:

0.0819

Alfa

AF:

0.107

Hom.:

645

Bravo

AF:

0.108

Asia WGS

AF:

0.0670

AC:

232

AN:

3478

EpiCase

AF:

0.105

EpiControl

AF:

0.104

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

C5-related disorder

Benign:1

Apr 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.2

DANN

Benign

0.47

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