1-22636978-A-G

Variant names:

• chr1-22636978-A-G
• rs2935542
• NM_015991.4:c.-8+276A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015991.4(C1QA):​c.-8+276A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 155,230 control chromosomes in the GnomAD database, including 793 homozygotes. 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: 𝑓 0.096 (782 hom., cov: 32)
  • Exomes 𝑓: 0.069 (11 hom.)
• Consequence: C1QA NM_015991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 16 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):

• C1Q deficiency

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

ENSG00000289692 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QA	NM_015991.4	MANE Select	c.-8+276A>G		intron	N/A	NP_057075.1
	C1QA	NM_001347465.2		c.-28+276A>G		intron	N/A	NP_001334394.1
	C1QA	NM_001347466.2		c.-8+118A>G		intron	N/A	NP_001334395.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QA	ENST00000374642.8	TSL:1 MANE Select	c.-8+276A>G		intron	N/A	ENSP00000363773.3
	C1QA	ENST00000402322.2	TSL:1	c.-28+276A>G		intron	N/A	ENSP00000385564.1
	ENSG00000289692	ENST00000695747.1		c.-8+276A>G		intron	N/A	ENSP00000512140.1

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14658 AN: 152008 Hom.: 780 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.0707

Gnomad ASJ AF: 0.0821

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0920

GnomAD4 exome AF: 0.0689 AC: 214 AN: 3104 Hom.: 11 AF XY: 0.0731 AC XY: 118 AN XY: 1614

African (AFR) AF: 0.0625 AC: 1 AN: 16

American (AMR) AF: 0.0561 AC: 33 AN: 588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26

East Asian (EAS) AF: 0.147 AC: 5 AN: 34

South Asian (SAS) AF: 0.120 AC: 18 AN: 150

European-Finnish (FIN) AF: 0.130 AC: 7 AN: 54

Middle Eastern (MID) AF: 0.100 AC: 1 AN: 10

European-Non Finnish (NFE) AF: 0.0669 AC: 141 AN: 2108

Other (OTH) AF: 0.0678 AC: 8 AN: 118

GnomAD4 genome AF: 0.0964 AC: 14672 AN: 152126 Hom.: 782 Cov.: 32 AF XY: 0.0995 AC XY: 7402 AN XY: 74370

African (AFR) AF: 0.109 AC: 4543 AN: 41506

American (AMR) AF: 0.0709 AC: 1084 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0821 AC: 285 AN: 3470

East Asian (EAS) AF: 0.142 AC: 732 AN: 5160

South Asian (SAS) AF: 0.150 AC: 723 AN: 4818

European-Finnish (FIN) AF: 0.115 AC: 1218 AN: 10598

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5692 AN: 67978

Other (OTH) AF: 0.0944 AC: 199 AN: 2108

Alfa AF: 0.0735 Hom.: 188

Bravo AF: 0.0933

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.41
PhyloP100		0.019
PromoterAI		0.032	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs2935542; hg19: chr1-22963471;