1-22638465-G-A

Position:

• chr1-22638465-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000374642.8(C1QA):​c.164-368G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,008 control chromosomes in the GnomAD database, including 24,493 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 0.54 (24493 hom., cov: 32)
• Consequence: C1QA ENST00000374642.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QA	NM_015991.4	c.164-368G>A		intron_variant		ENST00000374642.8	NP_057075.1
C1QA	NM_001347465.2	c.164-368G>A		intron_variant			NP_001334394.1
C1QA	NM_001347466.2	c.164-368G>A		intron_variant			NP_001334395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QA	ENST00000374642.8	c.164-368G>A		intron_variant		1	NM_015991.4	ENSP00000363773	P1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81442 AN: 151890 Hom.: 24437 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.504

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.537 AC: 81555 AN: 152008 Hom.: 24493 Cov.: 32 AF XY: 0.541 AC XY: 40192 AN XY: 74292

Gnomad4 AFR AF: 0.813

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.510

Alfa AF: 0.440 Hom.: 9059

Bravo AF: 0.557

Asia WGS AF: 0.649 AC: 2255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs292001; hg19: chr1-22964958; COSMIC: COSV65892057;