rs12756603

Variant names:

• chr1-22655383-A-G
• rs12756603
• NM_001378156.1:c.-24+2080A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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, Unknown Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000308848 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378156.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QB	NM_001378156.1	MANE Select	c.-24+2080A>G		intron	N/A	NP_001365085.1	D6R934
	C1QB	NM_000491.5		c.-18+2080A>G		intron	N/A	NP_000482.3
	C1QB	NM_001371184.3		c.-24+1223A>G		intron	N/A	NP_001358113.2	D6R934

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QB	ENST00000509305.6	TSL:1 MANE Select	c.-24+2080A>G		intron	N/A	ENSP00000423689.1	D6R934
	C1QB	ENST00000695760.1		c.-24+2080A>G		intron	N/A	ENSP00000512153.1	A0A8Q3WM25
	C1QB	ENST00000695754.1		c.-24+2015A>G		intron	N/A	ENSP00000512147.1	D6R934

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

African (AFR) AF: 0.326 AC: 13501 AN: 41440

American (AMR) AF: 0.118 AC: 1805 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3468

East Asian (EAS) AF: 0.274 AC: 1413 AN: 5166

South Asian (SAS) AF: 0.335 AC: 1608 AN: 4804

European-Finnish (FIN) AF: 0.100 AC: 1064 AN: 10596

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9175 AN: 68014

Other (OTH) AF: 0.191 AC: 403 AN: 2110

Alfa AF: 0.164 Hom.: 6545

Bravo AF: 0.201

Asia WGS AF: 0.319 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.75
PhyloP100		-0.39
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: rs12756603; hg19: chr1-22981876;