NM_001735.3:c.4806A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001735.3(C5):c.4806A>G(p.Lys1602Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 1,613,206 control chromosomes in the GnomAD database, including 3,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.058 ( 308 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3360 hom. )

Consequence

C5
NM_001735.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0580

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

complement component 5 deficiency
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

C5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 9-120953825-T-C is Benign according to our data. Variant chr9-120953825-T-C is described in ClinVar as Benign. ClinVar VariationId is 402450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.058 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001735.3 link	c.4806A>G	p.Lys1602Lys	synonymous_variant	Exon 40 of 41	ENST00000223642.3	NP_001726.2	P01031
C5	NM_001317163.2 link	c.4824A>G	p.Lys1608Lys	synonymous_variant	Exon 40 of 41		NP_001304092.1	P01031A0A8Q3SID6Q59GS8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3 link	c.4806A>G	p.Lys1602Lys	synonymous_variant	Exon 40 of 41	1	NM_001735.3	ENSP00000223642.1		P01031

Frequencies

GnomAD3 genomes

AF:

0.0580

AC:

8825

AN:

152190

Hom.:

303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0626

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0595

Gnomad ASJ

AF:

0.0628

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0742

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0650

Gnomad OTH

AF:

0.0570

GnomAD2 exomes

AF:

0.0571

AC:

14348

AN:

251378

AF XY:

0.0572

show subpopulations

Gnomad AFR exome

AF:

0.0642

Gnomad AMR exome

AF:

0.0599

Gnomad ASJ exome

AF:

0.0648

Gnomad EAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.0152

Gnomad NFE exome

AF:

0.0686

Gnomad OTH exome

AF:

0.0584

GnomAD4 exome

AF:

0.0643

AC:

93873

AN:

1460898

Hom.:

3360

Cov.:

AF XY:

0.0645

AC XY:

46892

AN XY:

726806

show subpopulations

African (AFR)

AF:

0.0652

AC:

2180

AN:

33456

American (AMR)

AF:

0.0592

AC:

2646

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0620

AC:

1620

AN:

26132

East Asian (EAS)

AF:

0.000907

AC:

AN:

39684

South Asian (SAS)

AF:

0.0678

AC:

5845

AN:

86242

European-Finnish (FIN)

AF:

0.0168

AC:

898

AN:

53418

Middle Eastern (MID)

AF:

0.0631

AC:

364

AN:

5766

European-Non Finnish (NFE)

AF:

0.0688

AC:

76453

AN:

1111108

Other (OTH)

AF:

0.0635

AC:

3831

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

4270

8540

12810

17080

21350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2874

5748

8622

11496

14370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0581

AC:

8842

AN:

152308

Hom.:

308

Cov.:

AF XY:

0.0559

AC XY:

4160

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0630

AC:

2618

AN:

41552

American (AMR)

AF:

0.0592

AC:

906

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0628

AC:

218

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5194

South Asian (SAS)

AF:

0.0736

AC:

355

AN:

4824

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10624

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0650

AC:

4423

AN:

68028

Other (OTH)

AF:

0.0573

AC:

121

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

425

850

1275

1700

2125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0670

Hom.:

550

Bravo

AF:

0.0616

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

EpiCase

AF:

0.0703

EpiControl

AF:

0.0713

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

2.0

(source)

DANN

Benign

0.53

PhyloP100

0.058

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over