rs12756603

Positions:

• chr1-22655383-A-G

Variant summary

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

The NM_001378156.1(C1QB):​c.-24+2080A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,100 control chromosomes in the GnomAD database, including 3,655 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 0.20 (3655 hom., cov: 32)
• Consequence: C1QB NM_001378156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QB	NM_001378156.1	c.-24+2080A>G		intron_variant		ENST00000509305.6	NP_001365085.1
C1QB	NM_000491.5	c.-18+2080A>G		intron_variant			NP_000482.3
C1QB	NM_001371184.3	c.-24+1223A>G		intron_variant			NP_001358113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QB	ENST00000509305.6	c.-24+2080A>G		intron_variant		1	NM_001378156.1	ENSP00000423689.1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29981 AN: 151982 Hom.: 3649 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.197 AC: 30026 AN: 152100 Hom.: 3655 Cov.: 32 AF XY: 0.196 AC XY: 14553 AN XY: 74354

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.191

Alfa AF: 0.153 Hom.: 3103

Bravo AF: 0.201

Asia WGS AF: 0.319 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.75

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: rs12756603; hg19: chr1-22981876;