dbSNP rs631090: C1QB:c.181+267T>C (chr1-22659910-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001378156.1(C1QB):c.181+267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,088 control chromosomes in the GnomAD database, including 4,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 4987 hom., cov: 32)

Consequence

C1QB
NM_001378156.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.296

Publications

24 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-22659910-T-C is Benign according to our data. Variant chr1-22659910-T-C is described in ClinVar as Benign. ClinVar VariationId is 1288576.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
C1QB	NM_001378156.1 link	c.181+267T>C	intron_variant	Intron 2 of 2	ENST00000509305.6	NP_001365085.1
C1QB	NM_000491.5 link	c.187+267T>C	intron_variant	Intron 2 of 2		NP_000482.3	P02746A0A024RAB9
C1QB	NM_001371184.3 link	c.181+267T>C	intron_variant	Intron 3 of 3		NP_001358113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QB	ENST00000509305.6 link	c.181+267T>C		intron_variant	Intron 2 of 2	1	NM_001378156.1	ENSP00000423689.1		D6R934

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29391

AN:

151970

Hom.:

4980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0854

Gnomad EAS

AF:

0.243

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.0976

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0700

Gnomad OTH

AF:

0.182

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.193

AC:

29424

AN:

152088

Hom.:

4987

Cov.:

AF XY:

0.193

AC XY:

14366

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.455

AC:

18850

AN:

41448

American (AMR)

AF:

0.134

AC:

2053

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0854

AC:

296

AN:

3468

East Asian (EAS)

AF:

0.242

AC:

1248

AN:

5156

South Asian (SAS)

AF:

0.145

AC:

698

AN:

4818

European-Finnish (FIN)

AF:

0.0976

AC:

1034

AN:

10590

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0700

AC:

4763

AN:

68000

Other (OTH)

AF:

0.185

AC:

391

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1018

2036

3054

4072

5090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

280

560

840

1120

1400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.108

Hom.:

3035

Bravo

AF:

0.209

Asia WGS

AF:

0.196

AC:

684

AN:

3478

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

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.8

(source)

DANN

Benign

0.66

PhyloP100

-0.30

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over