Variant rs2271708 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000587.4(C7):c.382T>C(p.Cys128Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0114 in 1,613,254 control chromosomes in the GnomAD database, including 468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.012 ( 48 hom., cov: 32)

Exomes 𝑓: 0.011 ( 420 hom. )

Consequence

C7
NM_000587.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.55

Variant links:

Genes affected

C7 (HGNC:1346): (complement C7) This gene encodes a serum glycoprotein that forms a membrane attack complex together with complement components C5b, C6, C8, and C9 as part of the terminal complement pathway of the innate immune system. The protein encoded by this gene contains a cholesterol-dependent cytolysin/membrane attack complex/perforin-like (CDC/MACPF) domain and belongs to a large family of structurally related molecules that form pores involved in host immunity and bacterial pathogenesis. This protein initiates membrane attack complex formation by binding the C5b-C6 subcomplex and inserts into the phospholipid bilayer, serving as a membrane anchor. Mutations in this gene are associated with a rare disorder called C7 deficiency. [provided by RefSeq, Nov 2016]

C7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043652058).

BP6

Variant 5-40936439-T-C is Benign according to our data. Variant chr5-40936439-T-C is described in ClinVar as [Benign]. Clinvar id is 1165525.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C7	NM_000587.4 linkuse as main transcript	c.382T>C	p.Cys128Arg	missense_variant	5/18	ENST00000313164.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C7	ENST00000313164.10 linkuse as main transcript	c.382T>C	p.Cys128Arg	missense_variant	5/18	1	NM_000587.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1903

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0575

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.0398

Gnomad SAS

AF:

0.0258

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00639

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.0255

AC:

6333

AN:

248440

Hom.:

268

AF XY:

0.0220

AC XY:

2968

AN XY:

134768

show subpopulations

Gnomad AFR exome

AF:

0.00175

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.00707

Gnomad EAS exome

AF:

0.0365

Gnomad SAS exome

AF:

0.0240

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.00659

Gnomad OTH exome

AF:

0.0154

GnomAD4 exome

AF:

0.0113

AC:

16540

AN:

1460956

Hom.:

420

Cov.:

AF XY:

0.0113

AC XY:

8240

AN XY:

726764

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.00770

Gnomad4 EAS exome

AF:

0.0435

Gnomad4 SAS exome

AF:

0.0246

Gnomad4 FIN exome

AF:

0.0144

Gnomad4 NFE exome

AF:

0.00581

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.0125

AC:

1900

AN:

152298

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1041

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00176

Gnomad4 AMR

AF:

0.0575

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.0395

Gnomad4 SAS

AF:

0.0257

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.00639

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00934

Hom.:

Bravo

AF:

0.0154

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00101

AC:

ESP6500EA

AF:

0.00744

AC:

ExAC

AF:

0.0223

AC:

2697

Asia WGS

AF:

0.0350

AC:

123

AN:

3478

EpiCase

AF:

0.00524

EpiControl

AF:

0.00504

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Pathogenic

0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.43

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.5

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.33

MPC

0.16

ClinPred

0.033

GERP RS

5.0

Varity_R

0.94

gMVP

0.97

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