1-22645399-A-G

Variant names:

• chr1-22645399-A-G
• rs294185
• NM_172369.5:c.181+1195A>G

Variant summary

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

The NM_172369.5(C1QC):​c.181+1195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,952 control chromosomes in the GnomAD database, including 22,486 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 (22486 hom., cov: 31)
• Consequence: C1QC NM_172369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199
• Publications: 11 publications found

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 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QC	NM_172369.5	c.181+1195A>G		intron_variant	Intron 2 of 2	ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3	c.181+1195A>G		intron_variant	Intron 2 of 2		NP_001107573.1
C1QC	NM_001347619.2	c.181+1195A>G		intron_variant	Intron 2 of 2		NP_001334548.1
C1QC	NM_001347620.2	c.-87+1685A>G		intron_variant	Intron 1 of 1		NP_001334549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QC	ENST00000374640.9	c.181+1195A>G		intron_variant	Intron 2 of 2	1	NM_172369.5	ENSP00000363771.4

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77363 AN: 151834 Hom.: 22450 Cov.: 31

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.510 AC: 77441 AN: 151952 Hom.: 22486 Cov.: 31 AF XY: 0.509 AC XY: 37804 AN XY: 74276

African (AFR) AF: 0.800 AC: 33166 AN: 41458

American (AMR) AF: 0.483 AC: 7385 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1181 AN: 3466

East Asian (EAS) AF: 0.580 AC: 2988 AN: 5152

South Asian (SAS) AF: 0.436 AC: 2093 AN: 4800

European-Finnish (FIN) AF: 0.363 AC: 3832 AN: 10564

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25427 AN: 67912

Other (OTH) AF: 0.487 AC: 1027 AN: 2110

Alfa AF: 0.417 Hom.: 62871

Bravo AF: 0.534

Asia WGS AF: 0.526 AC: 1829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.58
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs294185; hg19: chr1-22971892;