chr1-22644140-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_172369.5(C1QC):​c.117C>T​(p.Pro39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,584,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

C1QC
NM_172369.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.62
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 Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant 1-22644140-C-T is Benign according to our data. Variant chr1-22644140-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 739840.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.62 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
C1QCNM_172369.5 linkuse as main transcriptc.117C>T p.Pro39= synonymous_variant 2/3 ENST00000374640.9 NP_758957.2
C1QCNM_001114101.3 linkuse as main transcriptc.117C>T p.Pro39= synonymous_variant 2/3 NP_001107573.1
C1QCNM_001347619.2 linkuse as main transcriptc.117C>T p.Pro39= synonymous_variant 2/3 NP_001334548.1
C1QCNM_001347620.2 linkuse as main transcriptc.-87+426C>T intron_variant NP_001334549.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
C1QCENST00000374640.9 linkuse as main transcriptc.117C>T p.Pro39= synonymous_variant 2/31 NM_172369.5 ENSP00000363771 P1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000387
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000150
AC:
3
AN:
199642
Hom.:
0
AF XY:
0.0000187
AC XY:
2
AN XY:
106844
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000660
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000114
Gnomad OTH exome
AF:
0.000196
GnomAD4 exome
AF:
0.0000286
AC:
41
AN:
1432846
Hom.:
0
Cov.:
31
AF XY:
0.0000268
AC XY:
19
AN XY:
709490
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000337
Gnomad4 OTH exome
AF:
0.0000673
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152126
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000387
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000580
Hom.:
0
Bravo
AF:
0.0000302

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 09, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
4.2
DANN
Benign
0.82

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: rs772835925; hg19: chr1-22970633; COSMIC: COSV101009581; COSMIC: COSV101009581; API