rs672693

Variant names:

• chr1-22644953-G-A
• rs672693
• NM_172369.5:c.181+749G>A

Your query was ambiguous. Multiple possible variants found:

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

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+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
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172369.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QC	NM_172369.5	MANE Select	c.181+749G>A		intron	N/A	NP_758957.2	P02747
	C1QC	NM_001114101.3		c.181+749G>A		intron	N/A	NP_001107573.1	P02747
	C1QC	NM_001347619.2		c.181+749G>A		intron	N/A	NP_001334548.1	P02747

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QC	ENST00000374640.9	TSL:1 MANE Select	c.181+749G>A		intron	N/A	ENSP00000363771.4	P02747
	C1QC	ENST00000374637.1	TSL:3	c.181+749G>A		intron	N/A	ENSP00000363768.1	P02747
	C1QC	ENST00000374639.7	TSL:2	c.181+749G>A		intron	N/A	ENSP00000363770.3	P02747

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

African (AFR) AF: 0.551 AC: 22828 AN: 41406

American (AMR) AF: 0.451 AC: 6892 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3466

East Asian (EAS) AF: 0.382 AC: 1964 AN: 5148

South Asian (SAS) AF: 0.302 AC: 1452 AN: 4808

European-Finnish (FIN) AF: 0.363 AC: 3830 AN: 10550

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25196 AN: 67924

Other (OTH) AF: 0.420 AC: 883 AN: 2100

Alfa AF: 0.418 Hom.: 9738

Bravo AF: 0.441

Asia WGS AF: 0.361 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		0.060
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: rs672693; hg19: chr1-22971446;