rs11670330

Variant names:

• chr19-47309908-G-A
• rs11670330
• NM_001736.4:c.3+10G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-47309908-G-A
• chr19-47309908-G-C
• chr19-47309908-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821
• Publications: 11 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 (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	c.3+10G>A		intron_variant	Intron 1 of 1	ENST00000355085.4	NP_001727.2
C5AR1	XM_047439300.1	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	c.3+10G>A		intron_variant	Intron 1 of 1	1	NM_001736.4	ENSP00000347197.2
C5AR1	ENST00000594787.1	c.-470+2398G>A		intron_variant	Intron 2 of 3	5		ENSP00000470613.1

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49444 AN: 151872 Hom.: 8345 Cov.: 32

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

GnomAD2 exomes AF: 0.338 AC: 83870 AN: 247920 AF XY: 0.336

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 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.: 32 AF XY: 0.289 AC XY: 209860 AN XY: 725206

African (AFR) AF: 0.410 AC: 13625 AN: 33200

American (AMR) AF: 0.398 AC: 17666 AN: 44432

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8429 AN: 26008

East Asian (EAS) AF: 0.506 AC: 19813 AN: 39148

South Asian (SAS) AF: 0.438 AC: 37625 AN: 85884

European-Finnish (FIN) AF: 0.321 AC: 17138 AN: 53352

Middle Eastern (MID) AF: 0.276 AC: 1584 AN: 5748

European-Non Finnish (NFE) AF: 0.254 AC: 282097 AN: 1109542

Other (OTH) AF: 0.299 AC: 18013 AN: 60194

GnomAD4 genome AF: 0.325 AC: 49458 AN: 151990 Hom.: 8351 Cov.: 32 AF XY: 0.329 AC XY: 24438 AN XY: 74282

African (AFR) AF: 0.405 AC: 16802 AN: 41442

American (AMR) AF: 0.316 AC: 4829 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1116 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2500 AN: 5168

South Asian (SAS) AF: 0.430 AC: 2070 AN: 4818

European-Finnish (FIN) AF: 0.313 AC: 3310 AN: 10566

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17779 AN: 67956

Other (OTH) AF: 0.313 AC: 660 AN: 2110

Alfa AF: 0.268 Hom.: 2616

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
PhyloP100		-0.82
PromoterAI		-0.0068	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11670330; hg19: chr19-47813165; COSMIC: COSV61893207; COSMIC: COSV61893207;