Variant rs4467185 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 15/22 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

Variant links:

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]

C5AR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
C5AR1	NM_001736.4 linkuse as main transcript	c.4G>A	p.Asp2Asn	missense_variant, splice_region_variant	2/2	ENST00000355085.4	NP_001727.2
C5AR1	XM_047439300.1 linkuse as main transcript	c.106G>A	p.Asp36Asn	missense_variant, splice_region_variant	3/3		XP_047295256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5AR1	ENST00000355085.4 linkuse as main transcript	c.4G>A	p.Asp2Asn	missense_variant, splice_region_variant	2/2	1	NM_001736.4	ENSP00000347197	P1
C5AR1	ENST00000594787.1 linkuse as main transcript	c.-354G>A		splice_region_variant, 5_prime_UTR_variant	4/4	5		ENSP00000470613

Frequencies

GnomAD3 genomes

AF:

0.971

AC:

147685

AN:

152120

Hom.:

71738

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.982

AC:

244208

AN:

248698

Hom.:

119957

AF XY:

0.982

AC XY:

131949

AN XY:

134352

show subpopulations

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 SAS exome

AF:

0.984

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.:

AF XY:

0.985

AC XY:

707188

AN XY:

718306

show subpopulations

Gnomad4 AFR exome

AF:

0.933

Gnomad4 AMR exome

AF:

0.980

Gnomad4 ASJ exome

AF:

0.977

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.983

Gnomad4 FIN exome

AF:

0.996

Gnomad4 NFE exome

AF:

0.986

Gnomad4 OTH exome

AF:

0.979

GnomAD4 genome

AF:

0.971

AC:

147771

AN:

152238

Hom.:

71770

Cov.:

AF XY:

0.971

AC XY:

72258

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.933

Gnomad4 AMR

AF:

0.976

Gnomad4 ASJ

AF:

0.978

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.983

Gnomad4 FIN

AF:

0.996

Gnomad4 NFE

AF:

0.985

Gnomad4 OTH

AF:

0.959

Alfa

AF:

0.979

Hom.:

150648

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

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.28

MetaRNN

Benign

0.0000020

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.24

REVEL

Benign

0.023

Sift

Benign

0.38

Sift4G

Benign

0.066

Polyphen

0.0050

Vest4

0.018

MPC

0.34

ClinPred

0.0048

GERP RS

1.7

Varity_R

0.070

gMVP

0.26

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over