1-22637706-C-G

Variant names:

• chr1-22637706-C-G
• rs147435427
• NM_015991.4:c.90C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015991.4(C1QA):​c.90C>G​(p.Asp30Glu) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D30D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: C1QA NM_015991.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.38
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21414092).

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.90C>G	p.Asp30Glu	missense	Exon 2 of 3	NP_057075.1	P02745
	C1QA	NM_001347465.2		c.90C>G	p.Asp30Glu	missense	Exon 2 of 3	NP_001334394.1	P02745
	C1QA	NM_001347466.2		c.90C>G	p.Asp30Glu	missense	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.90C>G	p.Asp30Glu	missense	Exon 2 of 3	ENSP00000363773.3	P02745
	C1QA	ENST00000402322.2	TSL:1	c.90C>G	p.Asp30Glu	missense	Exon 2 of 3	ENSP00000385564.1	P02745
	ENSG00000289692	ENST00000695747.1		c.90C>G	p.Asp30Glu	missense	Exon 2 of 5	ENSP00000512140.1	A0A8Q3SI62

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.0050
DANN	Benign	0.90
DEOGEN2	Benign	0.091	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.9	L
PhyloP100		-5.4
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.84	N
REVEL	Uncertain	0.30
Sift	Benign	0.10	T
Sift4G	Benign	0.28	T
Polyphen		0.37	B
Vest4		0.15
MutPred		0.27		Loss of loop (P = 0.0603)
MVP		0.59
MPC		0.67
ClinPred		0.15	T
GERP RS		-9.4
PromoterAI		-0.0039	Neutral
Varity_R		0.060
gMVP		0.63
Mutation Taster		=95/5	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: rs147435427; hg19: chr1-22964199;