chr1-22659292-AGATGGATG-A

Variant names:

• chr1-22659292-AGATGGATG-A
• rs56917855
• NM_001378156.1:c.-23-119_-23-112delGATGGATG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001378156.1(C1QB):​c.-23-119_-23-112delGATGGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 647,968 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00064 (0 hom.)
• Consequence: C1QB NM_001378156.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.22
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QB	NM_001378156.1	c.-23-119_-23-112delGATGGATG		intron_variant	Intron 1 of 2	ENST00000509305.6	NP_001365085.1
C1QB	NM_000491.5	c.-17-119_-17-112delGATGGATG		intron_variant	Intron 1 of 2		NP_000482.3
C1QB	NM_001371184.3	c.-23-119_-23-112delGATGGATG		intron_variant	Intron 2 of 3		NP_001358113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QB	ENST00000509305.6	c.-23-147_-23-140delGATGGATG		intron_variant	Intron 1 of 2	1	NM_001378156.1	ENSP00000423689.1

Frequencies

GnomAD3 genomes AF: 0.00307 AC: 395 AN: 128756 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00207

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00111

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00417

Gnomad NFE AF: 0.000257

Gnomad OTH AF: 0.00566

GnomAD4 exome AF: 0.000642 AC: 333 AN: 519080 Hom.: 0 AF XY: 0.000567 AC XY: 155 AN XY: 273576

African (AFR) AF: 0.0108 AC: 154 AN: 14198

American (AMR) AF: 0.000852 AC: 23 AN: 26992

Ashkenazi Jewish (ASJ) AF: 0.0000623 AC: 1 AN: 16064

East Asian (EAS) AF: 0.000269 AC: 7 AN: 25978

South Asian (SAS) AF: 0.000442 AC: 22 AN: 49816

European-Finnish (FIN) AF: 0.0000269 AC: 1 AN: 37190

Middle Eastern (MID) AF: 0.00232 AC: 5 AN: 2156

European-Non Finnish (NFE) AF: 0.000245 AC: 78 AN: 318504

Other (OTH) AF: 0.00149 AC: 42 AN: 28182

GnomAD4 genome AF: 0.00308 AC: 397 AN: 128888 Hom.: 1 Cov.: 0 AF XY: 0.00327 AC XY: 202 AN XY: 61730

African (AFR) AF: 0.0106 AC: 339 AN: 32054

American (AMR) AF: 0.00206 AC: 27 AN: 13078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3302

East Asian (EAS) AF: 0.00 AC: 0 AN: 3768

South Asian (SAS) AF: 0.00111 AC: 4 AN: 3596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7982

Middle Eastern (MID) AF: 0.00435 AC: 1 AN: 230

European-Non Finnish (NFE) AF: 0.000257 AC: 16 AN: 62250

Other (OTH) AF: 0.00558 AC: 10 AN: 1792

Alfa AF: 0.00 Hom.: 126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56917855; hg19: chr1-22985785;