rs4427917

Positions:

• chr19-47312458-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001736.4(C5AR1):​c.3+2560G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,048 control chromosomes in the GnomAD database, including 8,341 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8341 hom., cov: 32)
• Consequence: C5AR1 NM_001736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C5AR1	NM_001736.4	c.3+2560G>C		intron_variant		ENST00000355085.4	NP_001727.2
C5AR1	XM_047439300.1	c.105+4647G>C		intron_variant			XP_047295256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5AR1	ENST00000355085.4	c.3+2560G>C		intron_variant		1	NM_001736.4	ENSP00000347197	P1
C5AR1	ENST00000594787.1	c.-469-4011G>C		intron_variant		5		ENSP00000470613

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49447 AN: 151930 Hom.: 8335 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.317

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.325 AC: 49461 AN: 152048 Hom.: 8341 Cov.: 32 AF XY: 0.329 AC XY: 24437 AN XY: 74324

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.313

Alfa AF: 0.298 Hom.: 890

Bravo AF: 0.327

Asia WGS AF: 0.448 AC: 1556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.64
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs4427917; hg19: chr19-47815715;