rs869312973

Positions:

• chr12-8059829-A-ATC

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_004054.4(C3AR1):​c.355_356dupGA​(p.Asp119fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C3AR1 NM_004054.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.95

Genes affected

C3AR1 (HGNC:1319): (complement C3a receptor 1) C3a is an anaphylatoxin released during activation of the complement system. The protein encoded by this gene is an orphan G protein-coupled receptor for C3a. Binding of C3a by the encoded receptor activates chemotaxis, granule enzyme release, superoxide anion production, and bacterial opsonization. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-8059829-A-ATC is Pathogenic according to our data. Variant chr12-8059829-A-ATC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 222958.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3AR1	NM_004054.4	c.355_356dupGA	p.Asp119fs	frameshift_variant	2/2	ENST00000307637.5	NP_004045.1
C3AR1	NM_001326475.2	c.355_356dupGA	p.Asp119fs	frameshift_variant	2/2		NP_001313404.1
C3AR1	NM_001326477.2	c.355_356dupGA	p.Asp119fs	frameshift_variant	2/2		NP_001313406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3AR1	ENST00000307637.5	c.355_356dupGA	p.Asp119fs	frameshift_variant	2/2	1	NM_004054.4	ENSP00000302079.4
C3AR1	ENST00000546241.1	c.355_356dupGA	p.Asp119fs	frameshift_variant	2/2	4		ENSP00000444500.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hemolytic uremic syndrome, atypical, susceptibility to, 1 Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Nov 01, 2015

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs869312973; hg19: chr12-8212425;