Genetic Variant C1QB:c.-23-119_-23-112dupGATGGATG (chr1-22659292-A-AGATGGATG) – 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.-23-119_-23-112dupGATGGATG 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

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
C1QB	NM_001378156.1 link	c.-23-119_-23-112dupGATGGATG	intron_variant	Intron 1 of 2	ENST00000509305.6	NP_001365085.1
C1QB	NM_000491.5 link	c.-17-119_-17-112dupGATGGATG	intron_variant	Intron 1 of 2		NP_000482.3	P02746A0A024RAB9
C1QB	NM_001371184.3 link	c.-23-119_-23-112dupGATGGATG	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_-23-147insGATGGATG		intron_variant	Intron 1 of 2	1	NM_001378156.1	ENSP00000423689.1		D6R934

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

28105

AN:

128386

Hom.:

3414

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.244

AC:

3465

AN:

14172

American (AMR)

AF:

0.202

AC:

5457

AN:

26956

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

2104

AN:

16050

East Asian (EAS)

AF:

0.0252

AC:

655

AN:

26006

South Asian (SAS)

AF:

0.150

AC:

7466

AN:

49868

European-Finnish (FIN)

AF:

0.176

AC:

6531

AN:

37070

Middle Eastern (MID)

AF:

0.181

AC:

390

AN:

2158

European-Non Finnish (NFE)

AF:

0.183

AC:

58178

AN:

318048

Other (OTH)

AF:

0.189

AC:

5329

AN:

28152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

3139

6278

9417

12556

15695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.219

AC:

28136

AN:

128516

Hom.:

3418

Cov.:

AF XY:

0.216

AC XY:

13323

AN XY:

61572

show subpopulations

African (AFR)

AF:

0.261

AC:

8320

AN:

31916

American (AMR)

AF:

0.238

AC:

3104

AN:

13032

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

513

AN:

3296

East Asian (EAS)

AF:

0.0271

AC:

102

AN:

3766

South Asian (SAS)

AF:

0.141

AC:

505

AN:

3590

European-Finnish (FIN)

AF:

0.171

AC:

1359

AN:

7964

Middle Eastern (MID)

AF:

0.181

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.220

AC:

13661

AN:

62104

Other (OTH)

AF:

0.232

AC:

414

AN:

1788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

953

1906

2859

3812

4765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.107

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

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr1-22659292-A-AGATGGATG

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