rs700233

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 links:

ENSG00000289699 (HGNC:):

ENSG00000289699 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 402466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-39364452-G-A is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.360

AC:

90006

AN:

249768

Hom.:

17503

AF XY:

0.368

AC XY:

49696

AN XY:

134982

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 SAS exome

AF:

0.361

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

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.352

Gnomad4 ASJ exome

AF:

0.462

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.357

Gnomad4 FIN exome

AF:

0.372

Gnomad4 NFE exome

AF:

0.403

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.352

AC:

53598

AN:

152064

Hom.:

9967

Cov.:

AF XY:

0.353

AC XY:

26204

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.0708

Gnomad4 SAS

AF:

0.359

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.412

Gnomad4 OTH

AF:

0.412

Alfa

AF:

0.395

Hom.:

19854

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

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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 -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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

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

Varity_R

0.031

gMVP

0.28

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