rs291982

Variant names:

• chr1-22655913-C-A
• rs291982
• NM_001378156.1:c.-24+2610C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-22655913-C-A
• chr1-22655913-C-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+2610C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,044 control chromosomes in the GnomAD database, including 25,670 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 0.56 (25670 hom., cov: 32)
• Consequence: C1QB NM_001378156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 3 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QB	NM_001378156.1	c.-24+2610C>A		intron_variant	Intron 1 of 2	ENST00000509305.6	NP_001365085.1
C1QB	NM_000491.5	c.-18+2610C>A		intron_variant	Intron 1 of 2		NP_000482.3
C1QB	NM_001371184.3	c.-24+1753C>A		intron_variant	Intron 2 of 3		NP_001358113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QB	ENST00000509305.6	c.-24+2610C>A		intron_variant	Intron 1 of 2	1	NM_001378156.1	ENSP00000423689.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85468 AN: 151924 Hom.: 25627 Cov.: 32

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.563 AC: 85559 AN: 152044 Hom.: 25670 Cov.: 32 AF XY: 0.562 AC XY: 41745 AN XY: 74322

African (AFR) AF: 0.784 AC: 32544 AN: 41490

American (AMR) AF: 0.523 AC: 7979 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3470

East Asian (EAS) AF: 0.631 AC: 3262 AN: 5168

South Asian (SAS) AF: 0.609 AC: 2936 AN: 4824

European-Finnish (FIN) AF: 0.422 AC: 4457 AN: 10558

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31091 AN: 67960

Other (OTH) AF: 0.556 AC: 1172 AN: 2108

Alfa AF: 0.473 Hom.: 2065

Bravo AF: 0.579

Asia WGS AF: 0.655 AC: 2279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.32
PhyloP100		-0.11
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: rs291982; hg19: chr1-22982406;