Genetic Variant C1QB:c.-23-123_-23-112dupGATGGATGGATG (chr1-22659292-A-AGATGGATGGATG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001378156.1(C1QB):c.-23-123_-23-112dupGATGGATGGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00861 in 648,172 control chromosomes in the GnomAD database, including 105 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.011 ( 37 hom., cov: 0)

Exomes 𝑓: 0.0081 ( 68 hom. )

Consequence

C1QB
NM_001378156.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.22

Publications

0 publications found

Variant links:

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)

C1QB links:

ENSG00000308848 (HGNC:):

ENSG00000308848 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0107 (1374/128884) while in subpopulation AFR AF = 0.0179 (575/32056). AF 95% confidence interval is 0.0167. There are 37 homozygotes in GnomAd4. There are 617 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
C1QB	NM_001378156.1 link	c.-23-123_-23-112dupGATGGATGGATG	intron_variant	Intron 1 of 2	ENST00000509305.6	NP_001365085.1
C1QB	NM_000491.5 link	c.-17-123_-17-112dupGATGGATGGATG	intron_variant	Intron 1 of 2		NP_000482.3	P02746A0A024RAB9
C1QB	NM_001371184.3 link	c.-23-123_-23-112dupGATGGATGGATG	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 link	c.-23-148_-23-147insGATGGATGGATG		intron_variant	Intron 1 of 2	1	NM_001378156.1	ENSP00000423689.1		D6R934

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1365

AN:

128752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00478

Gnomad AMR

AF:

0.00880

Gnomad ASJ

AF:

0.00575

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.00445

Gnomad FIN

AF:

0.00413

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00940

Gnomad OTH

AF:

0.00962

GnomAD4 exome

AF:

0.00810

AC:

4208

AN:

519288

Hom.:

AF XY:

0.00795

AC XY:

2177

AN XY:

273684

show subpopulations

African (AFR)

AF:

0.0167

AC:

237

AN:

14198

American (AMR)

AF:

0.00733

AC:

198

AN:

26996

Ashkenazi Jewish (ASJ)

AF:

0.00678

AC:

109

AN:

16072

East Asian (EAS)

AF:

0.00196

AC:

AN:

26014

South Asian (SAS)

AF:

0.00581

AC:

290

AN:

49896

European-Finnish (FIN)

AF:

0.00629

AC:

234

AN:

37198

Middle Eastern (MID)

AF:

0.00649

AC:

AN:

2158

European-Non Finnish (NFE)

AF:

0.00878

AC:

2796

AN:

318564

Other (OTH)

AF:

0.00990

AC:

279

AN:

28192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

184

368

553

737

921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0107

AC:

1374

AN:

128884

Hom.:

Cov.:

AF XY:

0.00999

AC XY:

617

AN XY:

61734

show subpopulations

African (AFR)

AF:

0.0179

AC:

575

AN:

32056

American (AMR)

AF:

0.00879

AC:

115

AN:

13080

Ashkenazi Jewish (ASJ)

AF:

0.00575

AC:

AN:

3302

East Asian (EAS)

AF:

0.00212

AC:

AN:

3766

South Asian (SAS)

AF:

0.00445

AC:

AN:

3596

European-Finnish (FIN)

AF:

0.00413

AC:

AN:

7982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.00941

AC:

586

AN:

62244

Other (OTH)

AF:

0.0100

AC:

AN:

1792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

120

179

239

299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00167

Hom.:

126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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chr1-22659292-A-AGATGGATGGATG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

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