rs629409

chr1-22660245-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
C1QB	NM_001378156.1	c.182-567C>T		intron_variant		ENST00000509305.6
C1QB	NM_000491.5	c.188-567C>T		intron_variant
C1QB	NM_001371184.3	c.182-567C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QB	ENST00000509305.6	c.182-567C>T		intron_variant		1	NM_001378156.1	P2

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

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.239

Alfa AF: 0.177 Hom.: 1078

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

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: rs629409; hg19: chr1-22986738;