rs1143664

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001734.5(C1S):c.1167A>G(p.Pro389Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 1,613,332 control chromosomes in the GnomAD database, including 5,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 906 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4792 hom. )

Consequence

C1S
NM_001734.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.17

Publications

13 publications found

Variant links:

Genes affected

C1S (HGNC:1247): (complement C1s) This gene encodes a serine protease, which is a major constituent of the human complement subcomponent C1. C1s associates with two other complement components C1r and C1q in order to yield the first component of the serum complement system. Defects in this gene are the cause of selective C1s deficiency. [provided by RefSeq, Mar 2009]

C1S Gene-Disease associations (from GenCC):

Ehlers-Danlos syndrome, periodontal type 2
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
complement component C1s deficiency
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Ehlers-Danlos syndrome, periodontal type 1
Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
Ehlers-Danlos syndrome, periodontitis type
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

C1S links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 12-7067743-A-G is Benign according to our data. Variant chr12-7067743-A-G is described in ClinVar as Benign. ClinVar VariationId is 402440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1S	NM_001734.5 link	c.1167A>G	p.Pro389Pro	synonymous_variant	Exon 10 of 12	ENST00000360817.10	NP_001725.1	P09871
C1S	NM_201442.4 link	c.1167A>G	p.Pro389Pro	synonymous_variant	Exon 10 of 12		NP_958850.1	P09871
C1S	NM_001346850.2 link	c.666A>G	p.Pro222Pro	synonymous_variant	Exon 9 of 11		NP_001333779.1	P09871F8WCZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1S	ENST00000360817.10 link	c.1167A>G	p.Pro389Pro	synonymous_variant	Exon 10 of 12	1	NM_001734.5	ENSP00000354057.5		P09871

Frequencies

GnomAD3 genomes

AF:

0.0995

AC:

15130

AN:

152130

Hom.:

904

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0842

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.00211

Gnomad SAS

AF:

0.0901

Gnomad FIN

AF:

0.0615

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0738

Gnomad OTH

AF:

0.112

GnomAD2 exomes

AF:

0.0794

AC:

19953

AN:

251312

AF XY:

0.0800

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.0557

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.0683

Gnomad NFE exome

AF:

0.0785

Gnomad OTH exome

AF:

0.0949

GnomAD4 exome

AF:

0.0758

AC:

110782

AN:

1461084

Hom.:

4792

Cov.:

AF XY:

0.0765

AC XY:

55577

AN XY:

726892

show subpopulations

African (AFR)

AF:

0.171

AC:

5710

AN:

33448

American (AMR)

AF:

0.0587

AC:

2625

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

3675

AN:

26128

East Asian (EAS)

AF:

0.00118

AC:

AN:

39698

South Asian (SAS)

AF:

0.0886

AC:

7636

AN:

86232

European-Finnish (FIN)

AF:

0.0670

AC:

3581

AN:

53414

Middle Eastern (MID)

AF:

0.166

AC:

956

AN:

5764

European-Non Finnish (NFE)

AF:

0.0731

AC:

81281

AN:

1111306

Other (OTH)

AF:

0.0873

AC:

5271

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

5538

11075

16613

22150

27688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3022

6044

9066

12088

15110

<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:

0.0995

AC:

15150

AN:

152248

Hom.:

906

Cov.:

AF XY:

0.0982

AC XY:

7307

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.166

AC:

6876

AN:

41540

American (AMR)

AF:

0.0841

AC:

1286

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

490

AN:

3470

East Asian (EAS)

AF:

0.00212

AC:

AN:

5190

South Asian (SAS)

AF:

0.0902

AC:

435

AN:

4822

European-Finnish (FIN)

AF:

0.0615

AC:

653

AN:

10616

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0738

AC:

5021

AN:

68010

Other (OTH)

AF:

0.112

AC:

236

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

696

1392

2087

2783

3479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<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:

0.0852

Hom.:

1316

Bravo

AF:

0.104

Asia WGS

AF:

0.0720

AC:

248

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

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: MAF -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.17

(source)

DANN

Benign

0.28

PhyloP100

-2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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