19-47341024-C-T

Variant names:

• chr19-47341024-C-T
• rs369445731
• NM_001271749.2:c.225C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001271749.2(C5AR2):​c.225C>T​(p.His75His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000746 in 1,608,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: C5AR2 NM_001271749.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.741
• Publications: 0 publications found

Genes affected

C5AR2 (HGNC:4527): (complement C5a receptor 2) This gene encodes a G-protein coupled receptor 1 family member involved in the complement system of the innate immune response. Unlike classical G-protein coupled receptors, the encoded protein does not associate with intracellular G-proteins. It may instead modulate signal transduction through the beta-arrestin pathway, and may alternatively act as a decoy receptor. This gene may be involved in coronary artery disease and in the pathogenesis of sepsis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.741 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271749.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5AR2	NM_001271749.2	MANE Select	c.225C>T	p.His75His	synonymous	Exon 2 of 2	NP_001258678.1	Q9P296
	C5AR2	NM_001271750.2		c.225C>T	p.His75His	synonymous	Exon 2 of 2	NP_001258679.1	Q9P296
	C5AR2	NM_018485.3		c.225C>T	p.His75His	synonymous	Exon 2 of 2	NP_060955.1	Q9P296

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5AR2	ENST00000595464.3	TSL:1 MANE Select	c.225C>T	p.His75His	synonymous	Exon 2 of 2	ENSP00000472620.1	Q9P296
	C5AR2	ENST00000600626.1	TSL:1	c.225C>T	p.His75His	synonymous	Exon 2 of 2	ENSP00000471184.1	Q9P296
	C5AR2	ENST00000874258.1		c.225C>T	p.His75His	synonymous	Exon 3 of 3	ENSP00000544317.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152252 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000179 AC: 44 AN: 245364 AF XY: 0.000173

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000855

Gnomad NFE exome AF: 0.000241

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000742 AC: 108 AN: 1456130 Hom.: 0 Cov.: 31 AF XY: 0.0000745 AC XY: 54 AN XY: 724642

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.000543 AC: 26 AN: 47858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111890

Other (OTH) AF: 0.000298 AC: 18 AN: 60354

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152252 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74386

African (AFR) AF: 0.0000241 AC: 1 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.8
DANN	Benign	0.40
PhyloP100		0.74

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: rs369445731; hg19: chr19-47844281;