1-22638945-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015991.4(C1QA):​c.276A>T​(p.Gly92Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G92G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: C1QA NM_015991.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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):

• C1Q deficiency

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

ENSG00000289692 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.056).
• BP7: Synonymous conserved (PhyloP=-0.733 with no splicing effect.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448596 Hom.: 0 Cov.: 83 AF XY: 0.00000139 AC XY: 1 AN XY: 719478

African (AFR) AF: 0.00 AC: 0 AN: 33256

American (AMR) AF: 0.00 AC: 0 AN: 42068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39126

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84512

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105914

Other (OTH) AF: 0.00 AC: 0 AN: 59862

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-0.73
Mutation Taster		=98/2	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;