NM_172369.5:c.150C>T

Variant names:

• chr1-22644173-C-T
• rs1043458334
• NM_172369.5:c.150C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_172369.5(C1QC):​c.150C>T​(p.Tyr50Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,432,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: C1QC NM_172369.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 1-22644173-C-T is Benign according to our data. Variant chr1-22644173-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1111767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.23 with no splicing effect.

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.150C>T	p.Tyr50Tyr	synonymous	Exon 2 of 3	NP_758957.2	P02747
	C1QC	NM_001114101.3		c.150C>T	p.Tyr50Tyr	synonymous	Exon 2 of 3	NP_001107573.1	P02747
	C1QC	NM_001347619.2		c.150C>T	p.Tyr50Tyr	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.150C>T	p.Tyr50Tyr	synonymous	Exon 2 of 3	ENSP00000363771.4	P02747
	C1QC	ENST00000374637.1	TSL:3	c.150C>T	p.Tyr50Tyr	synonymous	Exon 2 of 3	ENSP00000363768.1	P02747
	C1QC	ENST00000374639.7	TSL:2	c.150C>T	p.Tyr50Tyr	synonymous	Exon 2 of 3	ENSP00000363770.3	P02747

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000150 AC: 3 AN: 200412 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000359

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000226

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000698 AC: 10 AN: 1432984 Hom.: 0 Cov.: 33 AF XY: 0.00000282 AC XY: 2 AN XY: 709456

African (AFR) AF: 0.00 AC: 0 AN: 33274

American (AMR) AF: 0.0000513 AC: 2 AN: 39002

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25396

East Asian (EAS) AF: 0.00 AC: 0 AN: 38764

South Asian (SAS) AF: 0.00 AC: 0 AN: 81512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51216

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5726

European-Non Finnish (NFE) AF: 0.00000546 AC: 6 AN: 1098684

Other (OTH) AF: 0.0000168 AC: 1 AN: 59410

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1043458334; hg19: chr1-22970666; COSMIC: COSV65889241; COSMIC: COSV65889241;