rs2271708

Variant names:

Variant summary

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

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 (★★).

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, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.55

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

complement component 7 deficiency
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

C7 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=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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
C7	NM_000587.4 link	c.382T>C	p.Cys128Arg	missense_variant	Exon 5 of 18	ENST00000313164.10	NP_000578.2	P10643Q05CI3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10 link	c.382T>C	p.Cys128Arg	missense_variant	Exon 5 of 18	1	NM_000587.4	ENSP00000322061.9		P10643

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

GnomAD2 exomes

AF:

0.0255

AC:

6333

AN:

248440

AF XY:

0.0220

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 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

African (AFR)

AF:

0.00179

AC:

AN:

33464

American (AMR)

AF:

0.101

AC:

4484

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.00770

AC:

201

AN:

26104

East Asian (EAS)

AF:

0.0435

AC:

1727

AN:

39688

South Asian (SAS)

AF:

0.0246

AC:

2116

AN:

86178

European-Finnish (FIN)

AF:

0.0144

AC:

768

AN:

53374

Middle Eastern (MID)

AF:

0.00850

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00581

AC:

6460

AN:

1111438

Other (OTH)

AF:

0.0112

AC:

675

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

754

1508

2263

3017

3771

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.0125

AC:

1900

AN:

152298

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1041

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

41568

American (AMR)

AF:

0.0575

AC:

878

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00721

AC:

AN:

3468

East Asian (EAS)

AF:

0.0395

AC:

205

AN:

5190

South Asian (SAS)

AF:

0.0257

AC:

124

AN:

4832

European-Finnish (FIN)

AF:

0.0136

AC:

144

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00639

AC:

435

AN:

68022

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

183

275

366

458

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00925

Hom.:

109

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:2

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

- -

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

(source)

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

PhyloP100

5.5

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

Mutation Taster

=66/34

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