rs631090

chr1-22659910-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001378156.1(C1QB):c.181+267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,088 control chromosomes in the GnomAD database, including 4,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (4987 hom., cov: 32)
• Consequence: C1QB NM_001378156.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.296

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-22659910-T-C is Benign according to our data. Variant chr1-22659910-T-C is described in ClinVar as [Benign]. Clinvar id is 1288576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QB	NM_001378156.1	c.181+267T>C		intron_variant		ENST00000509305.6
C1QB	NM_000491.5	c.187+267T>C		intron_variant
C1QB	NM_001371184.3	c.181+267T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QB	ENST00000509305.6	c.181+267T>C		intron_variant		1	NM_001378156.1	P2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29391 AN: 151970 Hom.: 4980 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0854

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0976

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.193 AC: 29424 AN: 152088 Hom.: 4987 Cov.: 32 AF XY: 0.193 AC XY: 14366 AN XY: 74348

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0854

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0976

Gnomad4 NFE AF: 0.0700

Gnomad4 OTH AF: 0.185

Alfa AF: 0.0932 Hom.: 1508

Bravo AF: 0.209

Asia WGS AF: 0.196 AC: 684 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.8
Dann	Benign	0.66

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: rs631090; hg19: chr1-22986403;