Variant 12-7064316-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001734.5(C1S):c.441C>T(p.Cys147=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0772 in 1,613,732 control chromosomes in the GnomAD database, including 5,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 774 hom., cov: 32)

Exomes 𝑓: 0.075 ( 4663 hom. )

Consequence

C1S
NM_001734.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.914

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 12-7064316-C-T is Benign according to our data. Variant chr12-7064316-C-T is described in ClinVar as [Benign]. Clinvar id is 402439.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-7064316-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.914 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
C1S	NM_001734.5 linkuse as main transcript	c.441C>T	p.Cys147=	synonymous_variant	5/12	ENST00000360817.10	NP_001725.1
C1S	NM_201442.4 linkuse as main transcript	c.441C>T	p.Cys147=	synonymous_variant	5/12		NP_958850.1
C1S	NM_001346850.2 linkuse as main transcript	c.-61C>T		5_prime_UTR_variant	4/11		NP_001333779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1S	ENST00000360817.10 linkuse as main transcript	c.441C>T	p.Cys147=	synonymous_variant	5/12	1	NM_001734.5	ENSP00000354057	P1

Frequencies

GnomAD3 genomes

AF:

0.0941

AC:

14298

AN:

152018

Hom.:

772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.0827

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0891

Gnomad FIN

AF:

0.0608

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0740

Gnomad OTH

AF:

0.108

GnomAD3 exomes

AF:

0.0779

AC:

19589

AN:

251466

Hom.:

904

AF XY:

0.0790

AC XY:

10730

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.0549

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.00163

Gnomad SAS exome

AF:

0.0907

Gnomad FIN exome

AF:

0.0683

Gnomad NFE exome

AF:

0.0787

Gnomad OTH exome

AF:

0.0938

GnomAD4 exome

AF:

0.0755

AC:

110334

AN:

1461596

Hom.:

4663

Cov.:

AF XY:

0.0762

AC XY:

55402

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.0579

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.00118

Gnomad4 SAS exome

AF:

0.0885

Gnomad4 FIN exome

AF:

0.0669

Gnomad4 NFE exome

AF:

0.0735

Gnomad4 OTH exome

AF:

0.0864

GnomAD4 genome

AF:

0.0941

AC:

14318

AN:

152136

Hom.:

774

Cov.:

AF XY:

0.0932

AC XY:

6930

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.0826

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0891

Gnomad4 FIN

AF:

0.0608

Gnomad4 NFE

AF:

0.0740

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.0841

Hom.:

721

Bravo

AF:

0.0975

Asia WGS

AF:

0.0710

AC:

245

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

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

-0.45

CADD

Benign

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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