rs294180

Variant names:

• chr1-22648301-C-A
• rs294180
• ENST00000836788.1:n.82-44G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-22648301-C-A
• chr1-22648301-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000836788.1(ENSG00000308848):​n.82-44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,794 control chromosomes in the GnomAD database, including 22,298 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (22298 hom., cov: 30)
• Consequence: ENSG00000308848 ENST00000836788.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 9 publications found

Genes affected

ENSG00000308848 (HGNC:):

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 Gene-Disease associations (from GenCC):

• C1Q deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QC	NM_172369.5	c.*518C>A		downstream_gene_variant		ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3	c.*518C>A		downstream_gene_variant			NP_001107573.1
C1QC	NM_001347619.2	c.*518C>A		downstream_gene_variant			NP_001334548.1
C1QC	NM_001347620.2	c.*518C>A		downstream_gene_variant			NP_001334549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QC	ENST00000374640.9	c.*518C>A		downstream_gene_variant		1	NM_172369.5	ENSP00000363771.4

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77013 AN: 151676 Hom.: 22262 Cov.: 30

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.484

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 77090 AN: 151794 Hom.: 22298 Cov.: 30 AF XY: 0.507 AC XY: 37602 AN XY: 74136

African (AFR) AF: 0.799 AC: 33117 AN: 41424

American (AMR) AF: 0.481 AC: 7325 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1170 AN: 3458

East Asian (EAS) AF: 0.578 AC: 2967 AN: 5134

South Asian (SAS) AF: 0.427 AC: 2048 AN: 4794

European-Finnish (FIN) AF: 0.363 AC: 3813 AN: 10518

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25288 AN: 67912

Other (OTH) AF: 0.485 AC: 1022 AN: 2106

Alfa AF: 0.290 Hom.: 771

Bravo AF: 0.532

Asia WGS AF: 0.526 AC: 1828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.095
DANN	Benign	0.75
PhyloP100		-1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs294180; hg19: chr1-22974794;