rs672693

Positions:

• chr1-22644953-G-A
• chr1-22644953-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172369.5(C1QC):​c.181+749G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,876 control chromosomes in the GnomAD database, including 14,319 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 0.42 (14319 hom., cov: 31)
• Consequence: C1QC NM_172369.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QC	NM_172369.5	c.181+749G>A		intron_variant		ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3	c.181+749G>A		intron_variant			NP_001107573.1
C1QC	NM_001347619.2	c.181+749G>A		intron_variant			NP_001334548.1
C1QC	NM_001347620.2	c.-87+1239G>A		intron_variant			NP_001334549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QC	ENST00000374640.9	c.181+749G>A		intron_variant		1	NM_172369.5	ENSP00000363771	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64423 AN: 151758 Hom.: 14292 Cov.: 31

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.425 AC: 64485 AN: 151876 Hom.: 14319 Cov.: 31 AF XY: 0.423 AC XY: 31409 AN XY: 74208

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.420

Alfa AF: 0.376 Hom.: 4326

Bravo AF: 0.441

Asia WGS AF: 0.361 AC: 1257 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	1.4
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs672693; hg19: chr1-22971446;