chr1-22637629-C-A

Variant names:

• chr1-22637629-C-A
• rs767510705
• NM_015991.4:c.13C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015991.4(C1QA):​c.13C>A​(p.Arg5Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: C1QA NM_015991.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.63
• Publications: 0 publications found

Genes affected

C1QA (HGNC:1241): (complement C1q A chain) This gene encodes the A-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. 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. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

C1QA Gene-Disease associations (from GenCC):

• systemic lupus erythematosus related to C1QA

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• C1Q deficiency

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000289692 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.01).
• BP7: Synonymous conserved (PhyloP=-5.63 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015991.4. 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
	C1QA	NM_015991.4	MANE Select	c.13C>A	p.Arg5Arg	synonymous	Exon 2 of 3	NP_057075.1	P02745
	C1QA	NM_001347465.2		c.13C>A	p.Arg5Arg	synonymous	Exon 2 of 3	NP_001334394.1	P02745
	C1QA	NM_001347466.2		c.13C>A	p.Arg5Arg	synonymous	Exon 2 of 3	NP_001334395.1	P02745

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QA	ENST00000374642.8	TSL:1 MANE Select	c.13C>A	p.Arg5Arg	synonymous	Exon 2 of 3	ENSP00000363773.3	P02745
	C1QA	ENST00000402322.2	TSL:1	c.13C>A	p.Arg5Arg	synonymous	Exon 2 of 3	ENSP00000385564.1	P02745
	ENSG00000289692	ENST00000695747.1		c.13C>A	p.Arg5Arg	synonymous	Exon 2 of 5	ENSP00000512140.1	A0A8Q3SI62

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461756 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727174

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.055
DANN	Benign	0.44
PhyloP100		-5.6
PromoterAI		0.0056	Neutral
Mutation Taster		=100/0	polymorphism

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: rs767510705; hg19: chr1-22964122; COSMIC: COSV65892478; COSMIC: COSV65892478;