dbSNP rs11670330: C5AR1:c.3+10G>A (chr19-47309908-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.821

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 (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 rank	MANE	Protein	UniProt
C5AR1	NM_001736.4 link	c.3+10G>A		intron_variant	Intron 1 of 1	ENST00000355085.4	NP_001727.2	P21730
C5AR1	XM_047439300.1 link	c.105+2097G>A		intron_variant	Intron 2 of 2		XP_047295256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5AR1	ENST00000355085.4 link	c.3+10G>A		intron_variant	Intron 1 of 1	1	NM_001736.4	ENSP00000347197.2		P21730
C5AR1	ENST00000594787.1 link	c.-470+2398G>A		intron_variant	Intron 2 of 3	5		ENSP00000470613.1		M0QZK7

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49444

AN:

151872

Hom.:

8345

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.289

AC XY:

209860

AN XY:

725206

show subpopulations

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.:

AF XY:

0.329

AC XY:

24438

AN XY:

74282

show subpopulations

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

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