rs11670330

chr19-47309908-G-Achr19-47309908-G-Cchr19-47309908-G-T

Variant summary

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

The NM_001736.4(C5AR1):c.3+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,609,498 control chromosomes in the GnomAD database, including 71,443 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 (8351 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63092 hom.)
• Consequence: C5AR1 NM_001736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821

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=-0.79).
• 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	UniProt
C5AR1	NM_001736.4	c.3+10G>A		intron_variant		ENST00000355085.4
C5AR1	XM_047439300.1	c.105+2097G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C5AR1	ENST00000355085.4	c.3+10G>A		intron_variant		1	NM_001736.4	P1
C5AR1	ENST00000594787.1	c.-470+2398G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49444 AN: 151872 Hom.: 8345 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.317

GnomAD3 exomes AF: 0.338 AC: 83870 AN: 247920 Hom.: 15120 AF XY: 0.336 AC XY: 45117 AN XY: 134142

Gnomad AFR exome AF: 0.404

Gnomad AMR exome AF: 0.406

Gnomad ASJ exome AF: 0.326

Gnomad EAS exome AF: 0.492

Gnomad SAS exome AF: 0.440

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.298

GnomAD4 exome AF: 0.285 AC: 415990 AN: 1457508 Hom.: 63092 Cov.: 32 AF XY: 0.289 AC XY: 209860 AN XY: 725206

Gnomad4 AFR exome AF: 0.410

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.324

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.325 AC: 49458 AN: 151990 Hom.: 8351 Cov.: 32 AF XY: 0.329 AC XY: 24438 AN XY: 74282

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: 0.313

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.313

Alfa AF: 0.259 Hom.: 1739

Bravo AF: 0.327

Asia WGS AF: 0.448 AC: 1557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.3
Dann	Benign	0.81

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: rs11670330; hg19: chr19-47813165; COSMIC: COSV61893207; COSMIC: COSV61893207;