Genetic Variant C1QB:c.-23-115_-23-112delGATG (chr1-22659292-AGATG-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001378156.1(C1QB):c.-23-115_-23-112delGATG 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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 -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	Effect	Exon rank	MANE	Protein	UniProt
C1QB	NM_001378156.1 link	c.-23-115_-23-112delGATG	intron_variant	Intron 1 of 2	ENST00000509305.6	NP_001365085.1
C1QB	NM_000491.5 link	c.-17-115_-17-112delGATG	intron_variant	Intron 1 of 2		NP_000482.3	P02746A0A024RAB9
C1QB	NM_001371184.3 link	c.-23-115_-23-112delGATG	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.-23-147_-23-144delGATG		intron_variant	Intron 1 of 2	1	NM_001378156.1	ENSP00000423689.1		D6R934

Frequencies

GnomAD3 genomes

AF:

0.0838

AC:

10785

AN:

128634

Hom.:

467

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0647

AC:

917

AN:

14178

American (AMR)

AF:

0.0515

AC:

1388

AN:

26942

Ashkenazi Jewish (ASJ)

AF:

0.116

AC:

1859

AN:

16000

East Asian (EAS)

AF:

0.148

AC:

3826

AN:

25900

South Asian (SAS)

AF:

0.171

AC:

8512

AN:

49680

European-Finnish (FIN)

AF:

0.0634

AC:

2353

AN:

37086

Middle Eastern (MID)

AF:

0.0915

AC:

197

AN:

2152

European-Non Finnish (NFE)

AF:

0.0831

AC:

26386

AN:

317616

Other (OTH)

AF:

0.0933

AC:

2622

AN:

28102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

2028

4056

6083

8111

10139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0840

AC:

10811

AN:

128768

Hom.:

468

Cov.:

AF XY:

0.0827

AC XY:

5101

AN XY:

61688

show subpopulations

African (AFR)

AF:

0.0682

AC:

2184

AN:

32028

American (AMR)

AF:

0.0606

AC:

792

AN:

13070

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

418

AN:

3296

East Asian (EAS)

AF:

0.0712

AC:

268

AN:

3764

South Asian (SAS)

AF:

0.181

AC:

649

AN:

3588

European-Finnish (FIN)

AF:

0.0589

AC:

470

AN:

7974

Middle Eastern (MID)

AF:

0.0652

AC:

AN:

230

European-Non Finnish (NFE)

AF:

0.0911

AC:

5665

AN:

62192

Other (OTH)

AF:

0.101

AC:

181

AN:

1794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

427

854

1280

1707

2134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0401

Hom.:

126

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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1-22659292-AGATGGATGGATGGATGGATG-AGATGGATGGATGGATG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over