rs4467185

Variant names:

• chr19-47319781-G-A
• rs4467185
• NM_001736.4:c.4G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-47319781-G-A
• chr19-47319781-G-C
• chr19-47319781-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001736.4(C5AR1):​c.4G>A​(p.Asp2Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,594,666 control chromosomes in the GnomAD database, including 771,229 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.97 (71770 hom., cov: 31)
  • Exomes 𝑓: 0.98 (699459 hom.)
• Consequence: C5AR1 NM_001736.4 missense, splice_region
• Scores: Splicing: ADA: 0.0002932
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0422458E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5AR1	NM_001736.4	c.4G>A	p.Asp2Asn	missense_variant, splice_region_variant	Exon 2 of 2	ENST00000355085.4	NP_001727.2
C5AR1	XM_047439300.1	c.106G>A	p.Asp36Asn	missense_variant, splice_region_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.4G>A	p.Asp2Asn	missense_variant, splice_region_variant	Exon 2 of 2	1	NM_001736.4	ENSP00000347197.2
C5AR1	ENST00000594787.1	c.-354G>A		splice_region_variant	Exon 4 of 4	5		ENSP00000470613.1
C5AR1	ENST00000594787.1	c.-354G>A		5_prime_UTR_variant	Exon 4 of 4	5		ENSP00000470613.1

Frequencies

GnomAD3 genomes AF: 0.971 AC: 147685 AN: 152120 Hom.: 71738 Cov.: 31

Gnomad AFR AF: 0.933

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.976

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.983

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.958

GnomAD2 exomes AF: 0.982 AC: 244208 AN: 248698 AF XY: 0.982

Gnomad AFR exome AF: 0.933

Gnomad AMR exome AF: 0.980

Gnomad ASJ exome AF: 0.978

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.995

Gnomad NFE exome AF: 0.984

Gnomad OTH exome AF: 0.975

GnomAD4 exome AF: 0.985 AC: 1420342 AN: 1442428 Hom.: 699459 Cov.: 28 AF XY: 0.985 AC XY: 707188 AN XY: 718306

African (AFR) AF: 0.933 AC: 30882 AN: 33116

American (AMR) AF: 0.980 AC: 43638 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 25085 AN: 25670

East Asian (EAS) AF: 1.00 AC: 39585 AN: 39586

South Asian (SAS) AF: 0.983 AC: 84098 AN: 85566

European-Finnish (FIN) AF: 0.996 AC: 53005 AN: 53244

Middle Eastern (MID) AF: 0.923 AC: 5280 AN: 5720

European-Non Finnish (NFE) AF: 0.986 AC: 1080311 AN: 1095256

Other (OTH) AF: 0.979 AC: 58458 AN: 59736

GnomAD4 genome AF: 0.971 AC: 147771 AN: 152238 Hom.: 71770 Cov.: 31 AF XY: 0.971 AC XY: 72258 AN XY: 74418

African (AFR) AF: 0.933 AC: 38757 AN: 41552

American (AMR) AF: 0.976 AC: 14906 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3396 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5156 AN: 5156

South Asian (SAS) AF: 0.983 AC: 4741 AN: 4822

European-Finnish (FIN) AF: 0.996 AC: 10576 AN: 10622

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.985 AC: 67035 AN: 68022

Other (OTH) AF: 0.959 AC: 2025 AN: 2112

Alfa AF: 0.977 Hom.: 213954

Bravo AF: 0.967

TwinsUK AF: 0.985 AC: 3654

ALSPAC AF: 0.986 AC: 3801

ESP6500AA AF: 0.936 AC: 4126

ESP6500EA AF: 0.983 AC: 8456

ExAC AF: 0.982 AC: 119172

Asia WGS AF: 0.981 AC: 3412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.25
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.023
Sift	Benign	0.38	T
Sift4G	Benign	0.066	T
Polyphen		0.0050	B
Vest4		0.018
MPC		0.34
ClinPred		0.0048	T
GERP RS		1.7
Varity_R		0.070
gMVP		0.26
Mutation Taster		=87/13	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs4467185; hg19: chr19-47823038; COSMIC: COSV108194381;