rs913243

Positions:

• chr1-22653494-C-A
• chr1-22653494-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.-24+191C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,084 control chromosomes in the GnomAD database, including 14,184 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 0.43 (14184 hom., cov: 33)
• Consequence: C1QB NM_001378156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793

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=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QB	NM_001378156.1	c.-24+191C>A		intron_variant		ENST00000509305.6
C1QB	NM_000491.5	c.-18+191C>A		intron_variant
C1QB	NM_001371184.3	c.-177+191C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QB	ENST00000509305.6	c.-24+191C>A		intron_variant		1	NM_001378156.1	P2

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65364 AN: 151966 Hom.: 14168 Cov.: 33

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.430 AC: 65421 AN: 152084 Hom.: 14184 Cov.: 33 AF XY: 0.429 AC XY: 31886 AN XY: 74348

Gnomad4 AFR AF: 0.459

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.515

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.440

Alfa AF: 0.422 Hom.: 1689

Bravo AF: 0.434

Asia WGS AF: 0.510 AC: 1775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.4
DANN	Benign	0.83

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: rs913243; hg19: chr1-22979987;