Genetic Variant NM_015991.4:c.48G>A (chr1-22637664-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_015991.4(C1QA):c.48G>A(p.Ser16Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

C1QA
NM_015991.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.886

Publications

0 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):

systemic lupus erythematosus related to C1QA
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
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: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.016).

BP6

Variant 1-22637664-G-A is Benign according to our data. Variant chr1-22637664-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3606783.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.886 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015991.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1QA	NM_015991.4	MANE Select	c.48G>A	p.Ser16Ser	synonymous	Exon 2 of 3	NP_057075.1	P02745
C1QA	NM_001347465.2		c.48G>A	p.Ser16Ser	synonymous	Exon 2 of 3	NP_001334394.1	P02745
C1QA	NM_001347466.2		c.48G>A	p.Ser16Ser	synonymous	Exon 2 of 3	NP_001334395.1	P02745

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1QA	ENST00000374642.8	TSL:1 MANE Select	c.48G>A	p.Ser16Ser	synonymous	Exon 2 of 3	ENSP00000363773.3	P02745
C1QA	ENST00000402322.2	TSL:1	c.48G>A	p.Ser16Ser	synonymous	Exon 2 of 3	ENSP00000385564.1	P02745
ENSG00000289692	ENST00000695747.1		c.48G>A	p.Ser16Ser	synonymous	Exon 2 of 5	ENSP00000512140.1	A0A8Q3SI62

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727188

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111968

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.9

(source)

DANN

Benign

0.65

PhyloP100

0.89

PromoterAI

-0.0080

Neutral

(source)

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over