1-22642875-C-T

Variant names:

• chr1-22642875-C-T
• rs12404537
• ENST00000695747.1:c.493-760C>T

Variant summary

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

The ENST00000695747.1(ENSG00000289692):​c.493-760C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,286 control chromosomes in the GnomAD database, including 1,924 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 0.14 (1924 hom., cov: 33)
• Consequence: ENSG00000289692 ENST00000695747.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 8 publications found

Genes affected

ENSG00000289692 (HGNC:):

C1QC (HGNC:1245): (complement C1q C chain) This gene encodes the C-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. 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. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. [provided by RefSeq, Dec 2016]

C1QC Gene-Disease associations (from GenCC):

• C1Q deficiency

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289692	ENST00000695747.1	c.493-760C>T		intron_variant	Intron 3 of 4			ENSP00000512140.1
ENSG00000289692	ENST00000695748.1	c.493-1136C>T		intron_variant	Intron 3 of 3			ENSP00000512141.1
C1QC	ENST00000695749.1	c.-414C>T		upstream_gene_variant				ENSP00000512142.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21573 AN: 152168 Hom.: 1926 Cov.: 33

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0294

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.142 AC: 21573 AN: 152286 Hom.: 1924 Cov.: 33 AF XY: 0.143 AC XY: 10611 AN XY: 74448

African (AFR) AF: 0.0352 AC: 1463 AN: 41574

American (AMR) AF: 0.207 AC: 3173 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3470

East Asian (EAS) AF: 0.0295 AC: 153 AN: 5186

South Asian (SAS) AF: 0.152 AC: 733 AN: 4824

European-Finnish (FIN) AF: 0.174 AC: 1851 AN: 10612

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13237 AN: 67998

Other (OTH) AF: 0.152 AC: 321 AN: 2116

Alfa AF: 0.101 Hom.: 224

Bravo AF: 0.140

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.67
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12404537; hg19: chr1-22969368;