rs1570079690

Variant names:

• chr1-22644065-G-A
• rs1570079690
• NM_172369.5:c.42G>A

Variant summary

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

The ENST00000695747.1(ENSG00000289692):​c.627G>A​(p.Lys209Lys) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ENSG00000289692 ENST00000695747.1 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.44

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 Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-22644065-G-A is Benign according to our data. Variant chr1-22644065-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2051747.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.43 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QC	NM_172369.5	c.42G>A	p.Lys14Lys	synonymous_variant	Exon 2 of 3	ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3	c.42G>A	p.Lys14Lys	synonymous_variant	Exon 2 of 3		NP_001107573.1
C1QC	NM_001347619.2	c.42G>A	p.Lys14Lys	synonymous_variant	Exon 2 of 3		NP_001334548.1
C1QC	NM_001347620.2	c.-87+351G>A		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.42G>A	p.Lys14Lys	synonymous_variant	Exon 2 of 3	1	NM_172369.5	ENSP00000363771.4
ENSG00000289692	ENST00000695747.1	c.627G>A	p.Lys209Lys	splice_region_variant, synonymous_variant	Exon 5 of 5			ENSP00000512140.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 17, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1570079690; hg19: chr1-22970558;