rs172378

Variant names:

• chr1-22638945-A-G
• rs172378
• NM_015991.4:c.276A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-22638945-A-G
• chr1-22638945-A-C
• chr1-22638945-A-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.733
• Publications: 62 publications found

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

ENSG00000289692 (HGNC:):

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QA	NM_015991.4	MANE Select	c.276A>G	p.Gly92Gly	synonymous	Exon 3 of 3	NP_057075.1	P02745
	C1QA	NM_001347465.2		c.276A>G	p.Gly92Gly	synonymous	Exon 3 of 3	NP_001334394.1	P02745
	C1QA	NM_001347466.2		c.276A>G	p.Gly92Gly	synonymous	Exon 3 of 3	NP_001334395.1	P02745

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QA	ENST00000374642.8	TSL:1 MANE Select	c.276A>G	p.Gly92Gly	synonymous	Exon 3 of 3	ENSP00000363773.3	P02745
	C1QA	ENST00000402322.2	TSL:1	c.276A>G	p.Gly92Gly	synonymous	Exon 3 of 3	ENSP00000385564.1	P02745
	ENSG00000289692	ENST00000695747.1		c.276A>G	p.Gly92Gly	synonymous	Exon 3 of 5	ENSP00000512140.1	A0A8Q3SI62

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77782 AN: 151976 Hom.: 21690 Cov.: 33

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

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.: 83 AF XY: 0.423 AC XY: 304269 AN XY: 719314

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

GnomAD4 genome AF: 0.512 AC: 77891 AN: 152094 Hom.: 21743 Cov.: 33 AF XY: 0.518 AC XY: 38477 AN XY: 74342

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

Alfa AF: 0.424 Hom.: 62053

Bravo AF: 0.530

Asia WGS AF: 0.630 AC: 2188 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	C1Q deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		-0.73
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs172378; hg19: chr1-22965438; COSMIC: COSV65889459; COSMIC: COSV65889459;