1-22638465-G-A

Variant names:

• chr1-22638465-G-A
• rs292001
• NM_015991.4:c.164-368G>A

Variant summary

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

The NM_015991.4(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 NM_015991.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 31 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=-0.9).
• 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 rank	MANE	Protein	UniProt
C1QA	NM_015991.4	c.164-368G>A		intron_variant	Intron 2 of 2	ENST00000374642.8	NP_057075.1
C1QA	NM_001347465.2	c.164-368G>A		intron_variant	Intron 2 of 2		NP_001334394.1
C1QA	NM_001347466.2	c.164-368G>A		intron_variant	Intron 2 of 2		NP_001334395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QA	ENST00000374642.8	c.164-368G>A		intron_variant	Intron 2 of 2	1	NM_015991.4	ENSP00000363773.3
ENSG00000289692	ENST00000695747.1	c.164-368G>A		intron_variant	Intron 2 of 4			ENSP00000512140.1

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

African (AFR) AF: 0.813 AC: 33714 AN: 41478

American (AMR) AF: 0.540 AC: 8247 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1330 AN: 3468

East Asian (EAS) AF: 0.617 AC: 3185 AN: 5158

South Asian (SAS) AF: 0.608 AC: 2919 AN: 4802

European-Finnish (FIN) AF: 0.419 AC: 4417 AN: 10544

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26242 AN: 67966

Other (OTH) AF: 0.510 AC: 1077 AN: 2112

Alfa AF: 0.442 Hom.: 12279

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs292001; hg19: chr1-22964958; COSMIC: COSV65892057;