rs700233

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001737.5(C9):c.13C>T(p.Arg5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,600,716 control chromosomes in the GnomAD database, including 121,576 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.35 ( 9967 hom., cov: 32)

Exomes 𝑓: 0.39 ( 111609 hom. )

Consequence

C9
NM_001737.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.28

Publications

40 publications found

Variant links:

Genes affected

C9 (HGNC:1358): (complement C9) This gene encodes the final component of the complement system. It 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 component C9 deficiency. [provided by RefSeq, Feb 2009]

C9 Gene-Disease associations (from GenCC):

complement component 9 deficiency
Inheritance: Unknown, AR Classification: STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

C9 links:

ENSG00000289699 (HGNC:):

ENSG00000289699 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7780066E-4).

BP6

Variant 5-39364452-G-A is Benign according to our data. Variant chr5-39364452-G-A is described in ClinVar as Benign. ClinVar VariationId is 402466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C9	NM_001737.5 link	c.13C>T	p.Arg5Trp	missense_variant	Exon 1 of 11	ENST00000263408.5	NP_001728.1	P02748

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C9	ENST00000263408.5 link	c.13C>T	p.Arg5Trp	missense_variant	Exon 1 of 11	1	NM_001737.5	ENSP00000263408.4		P02748

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53587

AN:

151946

Hom.:

9971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.0706

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.417

GnomAD2 exomes

AF:

0.360

AC:

90006

AN:

249768

AF XY:

0.368

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.347

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.0552

Gnomad FIN exome

AF:

0.370

Gnomad NFE exome

AF:

0.414

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.386

AC:

559842

AN:

1448652

Hom.:

111609

Cov.:

AF XY:

0.388

AC XY:

279669

AN XY:

721376

show subpopulations

African (AFR)

AF:

0.253

AC:

8434

AN:

33284

American (AMR)

AF:

0.352

AC:

15746

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

12024

AN:

26030

East Asian (EAS)

AF:

0.101

AC:

3996

AN:

39662

South Asian (SAS)

AF:

0.357

AC:

30706

AN:

85918

European-Finnish (FIN)

AF:

0.372

AC:

19561

AN:

52634

Middle Eastern (MID)

AF:

0.501

AC:

2882

AN:

5754

European-Non Finnish (NFE)

AF:

0.403

AC:

443608

AN:

1100738

Other (OTH)

AF:

0.382

AC:

22885

AN:

59962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

14554

29108

43663

58217

72771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13312

26624

39936

53248

66560

<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:

0.352

AC:

53598

AN:

152064

Hom.:

9967

Cov.:

AF XY:

0.353

AC XY:

26204

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.258

AC:

10677

AN:

41458

American (AMR)

AF:

0.391

AC:

5979

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.461

AC:

1600

AN:

3468

East Asian (EAS)

AF:

0.0708

AC:

366

AN:

5172

South Asian (SAS)

AF:

0.359

AC:

1731

AN:

4826

European-Finnish (FIN)

AF:

0.373

AC:

3934

AN:

10554

Middle Eastern (MID)

AF:

0.500

AC:

146

AN:

292

European-Non Finnish (NFE)

AF:

0.412

AC:

27981

AN:

67996

Other (OTH)

AF:

0.412

AC:

869

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1768

3537

5305

7074

8842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.385

Hom.:

33756

Bravo

AF:

0.348

TwinsUK

AF:

0.393

AC:

1459

ALSPAC

AF:

0.397

AC:

1529

ESP6500AA

AF:

0.254

AC:

1121

ESP6500EA

AF:

0.414

AC:

3563

ExAC

AF:

0.361

AC:

43802

Asia WGS

AF:

0.234

AC:

819

AN:

3478

EpiCase

AF:

0.430

EpiControl

AF:

0.435

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 -

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

Significance:Benign

Review Status:no assertion criteria provided

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

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.019

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.016

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.50

MetaRNN

Benign

0.00018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-2.3

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.85

REVEL

Benign

0.049

Sift

Benign

0.21

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.021

MPC

0.034

ClinPred

0.012

GERP RS

-8.7

PromoterAI

-0.036

Neutral

(source)

Varity_R

0.031

gMVP

0.28

Mutation Taster

=98/2

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

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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