chr9-121017727-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001735.3(C5):c.1632C>T(p.Tyr544Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,611,088 control chromosomes in the GnomAD database, including 166,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 12470 hom., cov: 31)

Exomes 𝑓: 0.45 ( 153540 hom. )

Consequence

C5
NM_001735.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.50

Publications

39 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 -16 ACMG points.

BP6

Variant 9-121017727-G-A is Benign according to our data. Variant chr9-121017727-G-A is described in ClinVar as Benign. ClinVar VariationId is 402455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
C5	NM_001735.3 link	c.1632C>T	p.Tyr544Tyr	synonymous_variant	Exon 13 of 41	ENST00000223642.3	NP_001726.2
C5	NM_001317163.2 link	c.1650C>T	p.Tyr550Tyr	synonymous_variant	Exon 13 of 41		NP_001304092.1
C5	NM_001317164.2 link	c.1632C>T	p.Tyr544Tyr	synonymous_variant	Exon 13 of 21		NP_001304093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3 link	c.1632C>T	p.Tyr544Tyr	synonymous_variant	Exon 13 of 41	1	NM_001735.3	ENSP00000223642.1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55249

AN:

151880

Hom.:

12457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0853

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.509

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.408

GnomAD2 exomes

AF:

0.470

AC:

118062

AN:

251256

AF XY:

0.482

show subpopulations

Gnomad AFR exome

AF:

0.0729

Gnomad AMR exome

AF:

0.547

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.560

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.438

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.451

AC:

657998

AN:

1459090

Hom.:

153540

Cov.:

AF XY:

0.457

AC XY:

332121

AN XY:

725974

show subpopulations

African (AFR)

AF:

0.0713

AC:

2383

AN:

33444

American (AMR)

AF:

0.542

AC:

24217

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

13373

AN:

26120

East Asian (EAS)

AF:

0.533

AC:

21139

AN:

39682

South Asian (SAS)

AF:

0.629

AC:

54201

AN:

86198

European-Finnish (FIN)

AF:

0.485

AC:

25845

AN:

53276

Middle Eastern (MID)

AF:

0.508

AC:

2925

AN:

5762

European-Non Finnish (NFE)

AF:

0.439

AC:

486948

AN:

1109568

Other (OTH)

AF:

0.447

AC:

26967

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

18404

36808

55213

73617

92021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14752

29504

44256

59008

73760

<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:

0.364

AC:

55262

AN:

151998

Hom.:

12470

Cov.:

AF XY:

0.374

AC XY:

27771

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0850

AC:

3527

AN:

41498

American (AMR)

AF:

0.492

AC:

7508

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

1807

AN:

3468

East Asian (EAS)

AF:

0.559

AC:

2889

AN:

5170

South Asian (SAS)

AF:

0.625

AC:

3005

AN:

4806

European-Finnish (FIN)

AF:

0.509

AC:

5348

AN:

10514

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.435

AC:

29594

AN:

67962

Other (OTH)

AF:

0.409

AC:

860

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1567

3133

4700

6266

7833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

530

1060

1590

2120

2650

<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:

0.407

Hom.:

11725

Bravo

AF:

0.350

Asia WGS

AF:

0.531

AC:

1846

AN:

3478

EpiCase

AF:

0.446

EpiControl

AF:

0.441

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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: MAF

Jul 08, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.48

PhyloP100

3.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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