Variant rs1143664 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

C1S (HGNC:):

C1S links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 402440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-7067743-A-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
C1S	NM_001734.5 linkuse as main transcript	c.1167A>G	p.Pro389Pro	synonymous_variant	10/12	ENST00000360817.10	NP_001725.1	P09871
C1S	NM_201442.4 linkuse as main transcript	c.1167A>G	p.Pro389Pro	synonymous_variant	10/12		NP_958850.1	P09871
C1S	NM_001346850.2 linkuse as main transcript	c.666A>G	p.Pro222Pro	synonymous_variant	9/11		NP_001333779.1	P09871F8WCZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1S	ENST00000360817.10 linkuse as main transcript	c.1167A>G	p.Pro389Pro	synonymous_variant	10/12	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

GnomAD3 exomes

AF:

0.0794

AC:

19953

AN:

251312

Hom.:

965

AF XY:

0.0800

AC XY:

10863

AN XY:

135804

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 SAS exome

AF:

0.0907

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

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.0587

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.00118

Gnomad4 SAS exome

AF:

0.0886

Gnomad4 FIN exome

AF:

0.0670

Gnomad4 NFE exome

AF:

0.0731

Gnomad4 OTH exome

AF:

0.0873

GnomAD4 genome

AF:

0.0995

AC:

15150

AN:

152248

Hom.:

906

Cov.:

AF XY:

0.0982

AC XY:

7307

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.166

Gnomad4 AMR

AF:

0.0841

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0902

Gnomad4 FIN

AF:

0.0615

Gnomad4 NFE

AF:

0.0738

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.0834

Hom.:

973

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

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: MAF -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.17

DANN

Benign

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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