rs1865096

Positions:

• chr19-54885488-G-A
• chr19-54885488-G-C
• chr19-54885488-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002000.4(FCAR):​c.324G>A​(p.Arg108Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,096 control chromosomes in the GnomAD database, including 67,793 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 0.26 (5811 hom., cov: 31)
  • Exomes 𝑓: 0.29 (61982 hom.)
• Consequence: FCAR NM_002000.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

Genes affected

FCAR (HGNC:3608): (Fc alpha receptor) This gene is a member of the immunoglobulin gene superfamily and encodes a receptor for the Fc region of IgA. The receptor is a transmembrane glycoprotein present on the surface of myeloid lineage cells such as neutrophils, monocytes, macrophages, and eosinophils, where it mediates immunologic responses to pathogens. It interacts with IgA-opsonized targets and triggers several immunologic defense processes, including phagocytosis, antibody-dependent cell-mediated cytotoxicity, and stimulation of the release of inflammatory mediators. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

FCAR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=1.78 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCAR	NM_002000.4	c.324G>A	p.Arg108Arg	synonymous_variant	3/5	ENST00000355524.8	NP_001991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8	c.324G>A	p.Arg108Arg	synonymous_variant	3/5	1	NM_002000.4	ENSP00000347714.3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39758 AN: 151942 Hom.: 5802 Cov.: 31

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.286 AC: 418334 AN: 1461036 Hom.: 61982 Cov.: 34 AF XY: 0.288 AC XY: 209233 AN XY: 726850

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.478

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.277

Gnomad4 OTH exome AF: 0.284

GnomAD4 genome AF: 0.262 AC: 39782 AN: 152060 Hom.: 5811 Cov.: 31 AF XY: 0.271 AC XY: 20156 AN XY: 74336

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.292

Alfa AF: 0.270 Hom.: 8038

Bravo AF: 0.257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1865096; hg19: chr19-55396900;