1-22659910-T-C

Variant names:

• chr1-22659910-T-C
• rs631090
• NM_001378156.1:c.181+267T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 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 -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QB	NM_001378156.1	MANE Select	c.181+267T>C		intron	N/A	NP_001365085.1
	C1QB	NM_000491.5		c.187+267T>C		intron	N/A	NP_000482.3
	C1QB	NM_001371184.3		c.181+267T>C		intron	N/A	NP_001358113.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QB	ENST00000509305.6	TSL:1 MANE Select	c.181+267T>C		intron	N/A	ENSP00000423689.1
	C1QB	ENST00000695760.1		c.181+267T>C		intron	N/A	ENSP00000512153.1
	C1QB	ENST00000695754.1		c.181+267T>C		intron	N/A	ENSP00000512147.1

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

African (AFR) AF: 0.455 AC: 18850 AN: 41448

American (AMR) AF: 0.134 AC: 2053 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 296 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1248 AN: 5156

South Asian (SAS) AF: 0.145 AC: 698 AN: 4818

European-Finnish (FIN) AF: 0.0976 AC: 1034 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0700 AC: 4763 AN: 68000

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.108 Hom.: 3035

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

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.66
PhyloP100		-0.30
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: rs631090; hg19: chr1-22986403;