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GeneBe

19-47320392-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001736.4(C5AR1):c.615C>G(p.Val205=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,610,264 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0097 ( 28 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 36 hom. )

Consequence

C5AR1
NM_001736.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-47320392-C-G is Benign according to our data. Variant chr19-47320392-C-G is described in ClinVar as [Benign]. Clinvar id is 770291.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.33 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00972 (1481/152292) while in subpopulation AFR AF= 0.0335 (1391/41548). AF 95% confidence interval is 0.032. There are 28 homozygotes in gnomad4. There are 710 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 26 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C5AR1NM_001736.4 linkuse as main transcriptc.615C>G p.Val205= synonymous_variant 2/2 ENST00000355085.4
C5AR1XM_047439300.1 linkuse as main transcriptc.717C>G p.Val239= synonymous_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C5AR1ENST00000355085.4 linkuse as main transcriptc.615C>G p.Val205= synonymous_variant 2/21 NM_001736.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00962
AC:
1464
AN:
152174
Hom.:
26
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0332
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00347
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.00269
AC:
668
AN:
248642
Hom.:
18
AF XY:
0.00200
AC XY:
269
AN XY:
134698
show subpopulations
Gnomad AFR exome
AF:
0.0343
Gnomad AMR exome
AF:
0.00257
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000229
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000655
GnomAD4 exome
AF:
0.00110
AC:
1600
AN:
1457972
Hom.:
36
Cov.:
78
AF XY:
0.000972
AC XY:
705
AN XY:
725480
show subpopulations
Gnomad4 AFR exome
AF:
0.0335
Gnomad4 AMR exome
AF:
0.00241
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000417
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000702
Gnomad4 OTH exome
AF:
0.00408
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00972
AC:
1481
AN:
152292
Hom.:
28
Cov.:
32
AF XY:
0.00953
AC XY:
710
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0335
Gnomad4 AMR
AF:
0.00347
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.0104
Alfa
AF:
0.00326
Hom.:
5
Bravo
AF:
0.0113
Asia WGS
AF:
0.00693
AC:
24
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
0.20
Dann
Benign
0.61
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

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

Other links and lift over

dbSNP: rs61733735; hg19: chr19-47823649; API