19-47319863-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001736.4(C5AR1):​c.86C>A​(p.Thr29Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

C5AR1
NM_001736.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0490
Variant links:
Genes affected
C5AR1 (HGNC:1338): (complement C5a receptor 1) Enables G protein-coupled receptor activity and complement component C5a receptor activity. Involved in several processes, including complement component C5a signaling pathway; mRNA transcription by RNA polymerase II; and positive regulation of ERK1 and ERK2 cascade. Located in apical part of cell and basolateral plasma membrane. Biomarker of Alzheimer's disease; asthma; chronic obstructive pulmonary disease; rhinitis; and severe acute respiratory syndrome. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07234964).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C5AR1NM_001736.4 linkuse as main transcriptc.86C>A p.Thr29Asn missense_variant 2/2 ENST00000355085.4
C5AR1XM_047439300.1 linkuse as main transcriptc.188C>A p.Thr63Asn missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C5AR1ENST00000355085.4 linkuse as main transcriptc.86C>A p.Thr29Asn missense_variant 2/21 NM_001736.4 P1
C5AR1ENST00000594787.1 linkuse as main transcriptc.-272C>A 5_prime_UTR_variant 4/45

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
35
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 22, 2023The c.86C>A (p.T29N) alteration is located in exon 2 (coding exon 2) of the C5AR1 gene. This alteration results from a C to A substitution at nucleotide position 86, causing the threonine (T) at amino acid position 29 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.29
DANN
Benign
0.46
DEOGEN2
Benign
0.15
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.067
N
LIST_S2
Benign
0.47
T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.072
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.63
N
REVEL
Benign
0.021
Sift
Benign
0.21
T
Sift4G
Benign
0.35
T
Polyphen
0.17
B
Vest4
0.068
MutPred
0.33
Gain of relative solvent accessibility (P = 0.0522);
MVP
0.25
MPC
0.18
ClinPred
0.087
T
GERP RS
-2.2
Varity_R
0.045
gMVP
0.17

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-47823120; API