NM_001736.4:c.289G>T

Variant names:

• chr19-47320066-G-T
• rs1398113913
• NM_001736.4:c.289G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001736.4(C5AR1):​c.289G>T​(p.Val97Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: C5AR1 NM_001736.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

ACMG classification

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=0.083165675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5AR1	NM_001736.4	c.289G>T	p.Val97Leu	missense_variant	Exon 2 of 2	ENST00000355085.4	NP_001727.2
C5AR1	XM_047439300.1	c.391G>T	p.Val131Leu	missense_variant	Exon 3 of 3		XP_047295256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5AR1	ENST00000355085.4	c.289G>T	p.Val97Leu	missense_variant	Exon 2 of 2	1	NM_001736.4	ENSP00000347197.2
C5AR1	ENST00000594787.1	c.-69G>T		5_prime_UTR_variant	Exon 4 of 4	5		ENSP00000470613.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.0010
DANN	Benign	0.45
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.019
Sift	Benign	0.55	T
Sift4G	Benign	0.45	T
Polyphen		0.0040	B
Vest4		0.035
MutPred		0.64		Loss of catalytic residue at V97 (P = 0.1076);
MVP		0.26
MPC		0.15
ClinPred		0.056	T
GERP RS		-9.3
Varity_R		0.14
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1398113913; hg19: chr19-47823323;