1-22659292-AGATG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001378156.1(C1QB):c.-23-115_-23-112del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 646,424 control chromosomes in the GnomAD database, including 3,520 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (468 hom., cov: 0)
  • Exomes 𝑓: 0.093 (3052 hom.)
• Consequence: C1QB NM_001378156.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22

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 -10 ACMG points.

• BP6: Variant 1-22659292-AGATG-A is Benign according to our data. Variant chr1-22659292-AGATG-A is described in ClinVar as [Benign]. Clinvar id is 1252299.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QB	NM_001378156.1	c.-23-115_-23-112del		intron_variant		ENST00000509305.6
C1QB	NM_000491.5	c.-17-115_-17-112del		intron_variant
C1QB	NM_001371184.3	c.-23-115_-23-112del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QB	ENST00000509305.6	c.-23-115_-23-112del		intron_variant		1	NM_001378156.1	P2

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 10785 AN: 128634 Hom.: 467 Cov.: 0

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0630

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.0977

GnomAD4 exome AF: 0.0928 AC: 48060 AN: 517656 Hom.: 3052 AF XY: 0.0978 AC XY: 26681 AN XY: 272788

Gnomad4 AFR exome AF: 0.0647

Gnomad4 AMR exome AF: 0.0515

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.0634

Gnomad4 NFE exome AF: 0.0831

Gnomad4 OTH exome AF: 0.0933

GnomAD4 genome AF: 0.0840 AC: 10811 AN: 128768 Hom.: 468 Cov.: 0 AF XY: 0.0827 AC XY: 5101 AN XY: 61688

Gnomad4 AFR AF: 0.0682

Gnomad4 AMR AF: 0.0606

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.0712

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0589

Gnomad4 NFE AF: 0.0911

Gnomad4 OTH AF: 0.101

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

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: rs56917855; hg19: chr1-22985785;