rs13157656

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000587.4(C7):c.1759A>C(p.Thr587Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,611,870 control chromosomes in the GnomAD database, including 47,050 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.19 ( 3476 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43574 hom. )

Consequence

C7
NM_000587.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.26

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012661219).

BP6

Variant 5-40964750-A-C is Benign according to our data. Variant chr5-40964750-A-C is described in ClinVar as [Benign]. Clinvar id is 1169276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-40964750-A-C is described in Lovd as [Benign]. Variant chr5-40964750-A-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C7	NM_000587.4 link	c.1759A>C	p.Thr587Pro	missense_variant	Exon 14 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.1759A>C	p.Thr587Pro	missense_variant	Exon 14 of 18	1	NM_000587.4	ENSP00000322061.9		P10643

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29525

AN:

152074

Hom.:

3475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0623

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.197

GnomAD3 exomes

AF:

0.240

AC:

59740

AN:

248552

Hom.:

7842

AF XY:

0.250

AC XY:

33752

AN XY:

134830

show subpopulations

Gnomad AFR exome

AF:

0.0575

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.375

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.238

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.239

AC:

348979

AN:

1459678

Hom.:

43574

Cov.:

AF XY:

0.244

AC XY:

177151

AN XY:

726174

show subpopulations

Gnomad4 AFR exome

AF:

0.0549

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.244

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.374

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.237

GnomAD4 genome

AF:

0.194

AC:

29543

AN:

152192

Hom.:

3476

Cov.:

AF XY:

0.199

AC XY:

14805

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0622

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.239

Gnomad4 EAS

AF:

0.242

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.241

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.230

Hom.:

8863

Bravo

AF:

0.181

TwinsUK

AF:

0.235

AC:

871

ALSPAC

AF:

0.230

AC:

885

ESP6500AA

AF:

0.0641

AC:

239

ESP6500EA

AF:

0.235

AC:

1927

ExAC

AF:

0.239

AC:

28863

Asia WGS

AF:

0.314

AC:

1091

AN:

3478

EpiCase

AF:

0.241

EpiControl

AF:

0.236

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

not specified

Benign:1

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

1.2

DANN

Benign

0.74

DEOGEN2

Benign

0.020

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.61

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.80

REVEL

Benign

0.048

Sift

Benign

0.15

Sift4G

Benign

0.28

Polyphen

0.0010

Vest4

0.035

MPC

0.018

ClinPred

0.00090

GERP RS

-4.7

Varity_R

0.46

gMVP

0.63

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