9-120963693-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001735.3(C5):c.4266G>A(p.Ala1422Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,613,500 control chromosomes in the GnomAD database, including 2,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 888 hom., cov: 32)

Exomes 𝑓: 0.025 ( 2035 hom. )

Consequence

C5
NM_001735.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.648

Publications

16 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 9-120963693-C-T is Benign according to our data. Variant chr9-120963693-C-T is described in ClinVar as Benign. ClinVar VariationId is 1167627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.648 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001735.3 link	c.4266G>A	p.Ala1422Ala	synonymous_variant	Exon 34 of 41	ENST00000223642.3	NP_001726.2
C5	NM_001317163.2 link	c.4284G>A	p.Ala1428Ala	synonymous_variant	Exon 34 of 41		NP_001304092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3 link	c.4266G>A	p.Ala1422Ala	synonymous_variant	Exon 34 of 41	1	NM_001735.3	ENSP00000223642.1

Frequencies

GnomAD3 genomes

AF:

0.0711

AC:

10809

AN:

151976

Hom.:

884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0317

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.0442

Gnomad FIN

AF:

0.0215

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0578

GnomAD2 exomes

AF:

0.0450

AC:

11301

AN:

251344

AF XY:

0.0417

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0289

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.0253

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.0308

GnomAD4 exome

AF:

0.0249

AC:

36327

AN:

1461406

Hom.:

2035

Cov.:

AF XY:

0.0251

AC XY:

18282

AN XY:

727030

show subpopulations

African (AFR)

AF:

0.193

AC:

6448

AN:

33424

American (AMR)

AF:

0.0295

AC:

1319

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0186

AC:

487

AN:

26126

East Asian (EAS)

AF:

0.215

AC:

8542

AN:

39652

South Asian (SAS)

AF:

0.0403

AC:

3474

AN:

86236

European-Finnish (FIN)

AF:

0.0271

AC:

1446

AN:

53406

Middle Eastern (MID)

AF:

0.0229

AC:

132

AN:

5768

European-Non Finnish (NFE)

AF:

0.0109

AC:

12068

AN:

1111712

Other (OTH)

AF:

0.0399

AC:

2411

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

1528

3056

4583

6111

7639

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.0713

AC:

10838

AN:

152094

Hom.:

888

Cov.:

AF XY:

0.0712

AC XY:

5292

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.185

AC:

7682

AN:

41462

American (AMR)

AF:

0.0315

AC:

482

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3468

East Asian (EAS)

AF:

0.192

AC:

991

AN:

5174

South Asian (SAS)

AF:

0.0434

AC:

209

AN:

4812

European-Finnish (FIN)

AF:

0.0215

AC:

227

AN:

10578

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0155

AC:

1056

AN:

68000

Other (OTH)

AF:

0.0568

AC:

120

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

458

916

1374

1832

2290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0407

Hom.:

296

Bravo

AF:

0.0766

Asia WGS

AF:

0.113

AC:

391

AN:

3478

EpiCase

AF:

0.0139

EpiControl

AF:

0.0123

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

- -

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

-0.32

CADD

Benign

6.6

(source)

DANN

Benign

0.65

PhyloP100

-0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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