1-22638945-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015991.4(C1QA):c.276A>G(p.Gly92Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,600,412 control chromosomes in the GnomAD database, including 154,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 21743 hom., cov: 33)

Exomes 𝑓: 0.42 ( 133216 hom. )

Consequence

C1QA
NM_015991.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.733

Publications

62 publications found

Variant links:

Genes affected

C1QA (HGNC:1241): (complement C1q A chain) This gene encodes the A-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. 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. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

C1QA Gene-Disease associations (from GenCC):

C1Q deficiency
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

C1QA links:

ENSG00000289692 (HGNC:):

ENSG00000289692 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.061).

BP6

Variant 1-22638945-A-G is Benign according to our data. Variant chr1-22638945-A-G is described in ClinVar as Benign. ClinVar VariationId is 1167796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.733 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QA	NM_015991.4 link	c.276A>G	p.Gly92Gly	synonymous_variant	Exon 3 of 3	ENST00000374642.8	NP_057075.1	P02745A0A024RAG6
C1QA	NM_001347465.2 link	c.276A>G	p.Gly92Gly	synonymous_variant	Exon 3 of 3		NP_001334394.1	P02745A0A024RAG6
C1QA	NM_001347466.2 link	c.276A>G	p.Gly92Gly	synonymous_variant	Exon 3 of 3		NP_001334395.1	P02745A0A024RAG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QA	ENST00000374642.8 link	c.276A>G	p.Gly92Gly	synonymous_variant	Exon 3 of 3	1	NM_015991.4	ENSP00000363773.3		P02745
ENSG00000289692	ENST00000695747.1 link	c.276A>G	p.Gly92Gly	synonymous_variant	Exon 3 of 5			ENSP00000512140.1		A0A8Q3SI62

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77782

AN:

151976

Hom.:

21690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.732

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.532

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.590

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.487

GnomAD2 exomes

AF:

0.486

AC:

107980

AN:

222358

AF XY:

0.479

show subpopulations

Gnomad AFR exome

AF:

0.737

Gnomad AMR exome

AF:

0.624

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.425

Gnomad NFE exome

AF:

0.386

Gnomad OTH exome

AF:

0.455

GnomAD4 exome

AF:

0.420

AC:

608384

AN:

1448318

Hom.:

133216

Cov.:

AF XY:

0.423

AC XY:

304269

AN XY:

719314

show subpopulations

African (AFR)

AF:

0.747

AC:

24849

AN:

33248

American (AMR)

AF:

0.615

AC:

25837

AN:

42036

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

9721

AN:

25802

East Asian (EAS)

AF:

0.601

AC:

23510

AN:

39104

South Asian (SAS)

AF:

0.583

AC:

49295

AN:

84498

European-Finnish (FIN)

AF:

0.419

AC:

21898

AN:

52298

Middle Eastern (MID)

AF:

0.390

AC:

2235

AN:

5724

European-Non Finnish (NFE)

AF:

0.384

AC:

424774

AN:

1105760

Other (OTH)

AF:

0.439

AC:

26265

AN:

59848

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

25262

50524

75785

101047

126309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13710

27420

41130

54840

68550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.512

AC:

77891

AN:

152094

Hom.:

21743

Cov.:

AF XY:

0.518

AC XY:

38477

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.732

AC:

30410

AN:

41518

American (AMR)

AF:

0.532

AC:

8140

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1326

AN:

3468

East Asian (EAS)

AF:

0.590

AC:

3038

AN:

5152

South Asian (SAS)

AF:

0.607

AC:

2924

AN:

4820

European-Finnish (FIN)

AF:

0.418

AC:

4425

AN:

10576

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.385

AC:

26158

AN:

67950

Other (OTH)

AF:

0.492

AC:

1041

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1819

3637

5456

7274

9093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<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:

0.424

Hom.:

62053

Bravo

AF:

0.530

Asia WGS

AF:

0.630

AC:

2188

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 77% of patients studied by a panel of primary immunodeficiencies. Number of patients: 68. Only high quality variants are reported. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26017655, 12630757, 16465510, 16086173, 20332777) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

C1Q deficiency

Benign:1

Jul 14, 2021

Genome-Nilou Lab

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

-0.85

CADD

Benign

1.3

(source)

DANN

Benign

0.41

PhyloP100

-0.73

Mutation Taster

=56/44

polymorphism

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over