rs629409

Variant names:

• chr1-22660245-C-T
• rs629409
• NM_001378156.1:c.182-567C>T

Variant summary

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

The NM_001378156.1(C1QB):​c.182-567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,066 control chromosomes in the GnomAD database, including 5,325 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 0.24 (5325 hom., cov: 31)
• Consequence: C1QB NM_001378156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 10 publications found

Genes affected

C1QB (HGNC:1242): (complement C1q B chain) This gene encodes the B-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]

C1QB Gene-Disease associations (from GenCC):

• C1Q deficiency

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

ENSG00000308848 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QB	NM_001378156.1	c.182-567C>T		intron_variant	Intron 2 of 2	ENST00000509305.6	NP_001365085.1
C1QB	NM_000491.5	c.188-567C>T		intron_variant	Intron 2 of 2		NP_000482.3
C1QB	NM_001371184.3	c.182-567C>T		intron_variant	Intron 3 of 3		NP_001358113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QB	ENST00000509305.6	c.182-567C>T		intron_variant	Intron 2 of 2	1	NM_001378156.1	ENSP00000423689.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36117 AN: 151948 Hom.: 5298 Cov.: 31

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.238 AC: 36201 AN: 152066 Hom.: 5325 Cov.: 31 AF XY: 0.239 AC XY: 17788 AN XY: 74340

African (AFR) AF: 0.410 AC: 16998 AN: 41422

American (AMR) AF: 0.213 AC: 3256 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3468

East Asian (EAS) AF: 0.290 AC: 1498 AN: 5172

South Asian (SAS) AF: 0.309 AC: 1492 AN: 4822

European-Finnish (FIN) AF: 0.149 AC: 1573 AN: 10592

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9934 AN: 67980

Other (OTH) AF: 0.239 AC: 504 AN: 2112

Alfa AF: 0.172 Hom.: 1526

Bravo AF: 0.246

Asia WGS AF: 0.314 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.69
PhyloP100		-0.078
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: rs629409; hg19: chr1-22986738;