Menu
GeneBe

1-22644149-C-T

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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-8.42 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
C1QCNM_172369.5 linkuse as main transcriptc.126C>T p.Pro42= synonymous_variant 2/3 ENST00000374640.9
C1QCNM_001114101.3 linkuse as main transcriptc.126C>T p.Pro42= synonymous_variant 2/3
C1QCNM_001347619.2 linkuse as main transcriptc.126C>T p.Pro42= synonymous_variant 2/3
C1QCNM_001347620.2 linkuse as main transcriptc.-87+435C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C1QCENST00000374640.9 linkuse as main transcriptc.126C>T p.Pro42= synonymous_variant 2/31 NM_172369.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.281
AC:
42647
AN:
151928
Hom.:
6164
Cov.:
32
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.:
34
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.281
AC:
42674
AN:
152046
Hom.:
6164
Cov.:
32
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxNov 10, 2018- -
Benign, criteria provided, single submitterclinical testingInvitaeFeb 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.

Other links and lift over

dbSNP: rs15940; hg19: chr1-22970642; COSMIC: COSV65889640; COSMIC: COSV65889640; API