Variant 1-22644149-C-T 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_172369.5(C1QC):c.126C>T(p.Pro42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,584,918 control chromosomes in the GnomAD database, including 55,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6164 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49350 hom. )

Consequence

C1QC
NM_172369.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -8.42

Variant links:

Genes affected

C1QC (HGNC:1245): (complement C1q C chain) This gene encodes the C-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q is composed of 18 polypeptide chains which include 6 A-chains, 6 B-chains, and 6 C-chains. Each chain contains an N-terminal collagen-like region and a C-terminal C1q globular domain. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. [provided by RefSeq, Dec 2016]

C1QC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 1-22644149-C-T is Benign according to our data. Variant chr1-22644149-C-T is described in ClinVar as [Benign]. Clinvar id is 1167797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
C1QC	NM_172369.5 linkuse as main transcript	c.126C>T	p.Pro42=	synonymous_variant	2/3	ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3 linkuse as main transcript	c.126C>T	p.Pro42=	synonymous_variant	2/3		NP_001107573.1
C1QC	NM_001347619.2 linkuse as main transcript	c.126C>T	p.Pro42=	synonymous_variant	2/3		NP_001334548.1
C1QC	NM_001347620.2 linkuse as main transcript	c.-87+435C>T		intron_variant			NP_001334549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QC	ENST00000374640.9 linkuse as main transcript	c.126C>T	p.Pro42=	synonymous_variant	2/3	1	NM_172369.5	ENSP00000363771	P1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42647

AN:

151928

Hom.:

6164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.280

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.247

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.273

GnomAD3 exomes

AF:

0.270

AC:

54527

AN:

201684

Hom.:

7439

AF XY:

0.267

AC XY:

28829

AN XY:

107932

show subpopulations

Gnomad AFR exome

AF:

0.355

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.260

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.261

AC:

374256

AN:

1432872

Hom.:

49350

Cov.:

AF XY:

0.261

AC XY:

185265

AN XY:

709524

show subpopulations

Gnomad4 AFR exome

AF:

0.361

Gnomad4 AMR exome

AF:

0.303

Gnomad4 ASJ exome

AF:

0.254

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.280

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.257

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.281

AC:

42674

AN:

152046

Hom.:

6164

Cov.:

AF XY:

0.278

AC XY:

20652

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.279

Gnomad4 ASJ

AF:

0.251

Gnomad4 EAS

AF:

0.247

Gnomad4 SAS

AF:

0.286

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.257

Gnomad4 OTH

AF:

0.274

Alfa

AF:

0.266

Hom.:

2395

Bravo

AF:

0.290

Asia WGS

AF:

0.267

AC:

926

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.4

DANN

Benign

0.85

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