1-22636978-A-G

Position:

• chr1-22636978-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QA	NM_015991.4	c.-8+276A>G		intron_variant		ENST00000374642.8
C1QA	NM_001347465.2	c.-28+276A>G		intron_variant
C1QA	NM_001347466.2	c.-8+118A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QA	ENST00000374642.8	c.-8+276A>G		intron_variant		1	NM_015991.4	P1

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

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.0561

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.0669

Gnomad4 OTH exome AF: 0.0678

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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0709

Gnomad4 ASJ AF: 0.0821

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.0944

Alfa AF: 0.0672 Hom.: 117

Bravo AF: 0.0933

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs2935542; hg19: chr1-22963471;