rs760270842

Variant names:

• chr1-22644077-CCTG-C
• rs760270842
• NM_172369.5:c.65_67delTGC

Your query was ambiguous. Multiple possible variants found:

• chr1-22644077-CCTG-C
• chr1-22644077-CCTG-CCTGCTG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_172369.5(C1QC):​c.65_67delTGC​(p.Leu22del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000098 in 1,428,508 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: C1QC NM_172369.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.958

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]

ENSG00000289692 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QC	NM_172369.5	c.65_67delTGC	p.Leu22del	disruptive_inframe_deletion	Exon 2 of 3	ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3	c.65_67delTGC	p.Leu22del	disruptive_inframe_deletion	Exon 2 of 3		NP_001107573.1
C1QC	NM_001347619.2	c.65_67delTGC	p.Leu22del	disruptive_inframe_deletion	Exon 2 of 3		NP_001334548.1
C1QC	NM_001347620.2	c.-87+374_-87+376delTGC		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.65_67delTGC	p.Leu22del	disruptive_inframe_deletion	Exon 2 of 3	1	NM_172369.5	ENSP00000363771.4
ENSG00000289692	ENST00000695747.1	c.*11_*13delCTG		downstream_gene_variant				ENSP00000512140.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000980 AC: 14 AN: 1428508 Hom.: 0 AF XY: 0.00000707 AC XY: 5 AN XY: 707046

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000521

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000912

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 32

Alfa AF: 0.000153 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs760270842; hg19: chr1-22970570;