1-22659292-A-AGATG

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_-23-112dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 645,344 control chromosomes in the GnomAD database, including 7,484 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1799 hom., cov: 0)
  • Exomes 𝑓: 0.13 (5685 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-A-AGATG is Benign according to our data. Variant chr1-22659292-A-AGATG is described in ClinVar as [Benign]. Clinvar id is 1283735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.156 AC: 20089 AN: 128552 Hom.: 1791 Cov.: 0

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.0714

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.134 AC: 69363 AN: 516662 Hom.: 5685 AF XY: 0.133 AC XY: 36245 AN XY: 272296

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.0925

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.156 AC: 20112 AN: 128682 Hom.: 1799 Cov.: 0 AF XY: 0.157 AC XY: 9685 AN XY: 61632

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.161

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.152

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

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Computational scores

Source: dbNSFP v4.3

Splicing

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;