1-22659292-A-AGATGGATG

Variant summary

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

The NM_001378156.1(C1QB):c.-23-119_-23-112dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 646,996 control chromosomes in the GnomAD database, including 12,501 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3418 hom., cov: 0)
  • Exomes 𝑓: 0.17 (9083 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-AGATGGATG is Benign according to our data. Variant chr1-22659292-A-AGATGGATG is described in ClinVar as [Benign]. Clinvar id is 1269706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QB	NM_001378156.1	c.-23-119_-23-112dup		intron_variant		ENST00000509305.6
C1QB	NM_000491.5	c.-17-119_-17-112dup		intron_variant
C1QB	NM_001371184.3	c.-23-119_-23-112dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QB	ENST00000509305.6	c.-23-119_-23-112dup		intron_variant		1	NM_001378156.1	P2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 28105 AN: 128386 Hom.: 3414 Cov.: 0

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.173 AC: 89575 AN: 518480 Hom.: 9083 AF XY: 0.171 AC XY: 46830 AN XY: 273290

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0252

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.219 AC: 28136 AN: 128516 Hom.: 3418 Cov.: 0 AF XY: 0.216 AC XY: 13323 AN XY: 61572

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0271

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.232

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;