rs15940

Variant names:

• chr1-22644149-C-T
• rs15940
• NM_172369.5:c.126C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-22644149-C-T
• chr1-22644149-C-A
• chr1-22644149-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_172369.5(C1QC):​c.126C>T​(p.Pro42Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,584,918 control chromosomes in the GnomAD database, including 55,514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6164 hom., cov: 32)
  • Exomes 𝑓: 0.26 (49350 hom.)
• Consequence: C1QC NM_172369.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -8.42
• Publications: 16 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

ENSG00000289692 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 1-22644149-C-T is Benign according to our data. Variant chr1-22644149-C-T is described in ClinVar as Benign. ClinVar VariationId is 1167797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.42 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 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.126C>T	p.Pro42Pro	synonymous	Exon 2 of 3	NP_758957.2	P02747
	C1QC	NM_001114101.3		c.126C>T	p.Pro42Pro	synonymous	Exon 2 of 3	NP_001107573.1	P02747
	C1QC	NM_001347619.2		c.126C>T	p.Pro42Pro	synonymous	Exon 2 of 3	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.126C>T	p.Pro42Pro	synonymous	Exon 2 of 3	ENSP00000363771.4	P02747
	C1QC	ENST00000374637.1	TSL:3	c.126C>T	p.Pro42Pro	synonymous	Exon 2 of 3	ENSP00000363768.1	P02747
	C1QC	ENST00000374639.7	TSL:2	c.126C>T	p.Pro42Pro	synonymous	Exon 2 of 3	ENSP00000363770.3	P02747

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42647 AN: 151928 Hom.: 6164 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.273

GnomAD2 exomes AF: 0.270 AC: 54527 AN: 201684 AF XY: 0.267

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.248

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.261

GnomAD4 exome AF: 0.261 AC: 374256 AN: 1432872 Hom.: 49350 Cov.: 34 AF XY: 0.261 AC XY: 185265 AN XY: 709524

African (AFR) AF: 0.361 AC: 12003 AN: 33288

American (AMR) AF: 0.303 AC: 11826 AN: 39084

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 6459 AN: 25412

East Asian (EAS) AF: 0.261 AC: 10139 AN: 38786

South Asian (SAS) AF: 0.280 AC: 22840 AN: 81548

European-Finnish (FIN) AF: 0.219 AC: 11212 AN: 51094

Middle Eastern (MID) AF: 0.238 AC: 1363 AN: 5720

European-Non Finnish (NFE) AF: 0.257 AC: 282866 AN: 1098546

Other (OTH) AF: 0.262 AC: 15548 AN: 59394

GnomAD4 genome AF: 0.281 AC: 42674 AN: 152046 Hom.: 6164 Cov.: 32 AF XY: 0.278 AC XY: 20652 AN XY: 74308

African (AFR) AF: 0.346 AC: 14357 AN: 41480

American (AMR) AF: 0.279 AC: 4260 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 869 AN: 3468

East Asian (EAS) AF: 0.247 AC: 1271 AN: 5144

South Asian (SAS) AF: 0.286 AC: 1378 AN: 4822

European-Finnish (FIN) AF: 0.210 AC: 2224 AN: 10586

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17464 AN: 67950

Other (OTH) AF: 0.274 AC: 578 AN: 2110

Alfa AF: 0.266 Hom.: 2395

Bravo AF: 0.290

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.4
DANN	Benign	0.85
PhyloP100		-8.4
PromoterAI		0.0018	Neutral
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: rs15940; hg19: chr1-22970642; COSMIC: COSV65889640; COSMIC: COSV65889640;