rs10404456

Positions:

• chr19-47309643-C-T

Variant summary

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

The ENST00000594787.1(C5AR1):​c.-470+2133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,138 control chromosomes in the GnomAD database, including 32,568 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 0.65 (32568 hom., cov: 28)
• Consequence: C5AR1 ENST00000594787.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C5AR1	XM_047439300.1	c.105+1832C>T		intron_variant			XP_047295256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5AR1	ENST00000594787.1	c.-470+2133C>T		intron_variant		5		ENSP00000470613

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98478 AN: 151038 Hom.: 32537 Cov.: 28

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.645

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

GnomAD4 genome AF: 0.652 AC: 98551 AN: 151138 Hom.: 32568 Cov.: 28 AF XY: 0.649 AC XY: 47880 AN XY: 73784

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.657

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.650

Alfa AF: 0.708 Hom.: 75691

Bravo AF: 0.646

Asia WGS AF: 0.534 AC: 1860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10404456; hg19: chr19-47812900;