19-54885488-G-A

Variant names:

• chr19-54885488-G-A
• rs1865096
• NM_002000.4:c.324G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002000.4. 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
	FCAR	NM_002000.4	MANE Select	c.324G>A	p.Arg108Arg	synonymous	Exon 3 of 5	NP_001991.1	P24071-1
	FCAR	NM_133272.4		c.288G>A	p.Arg96Arg	synonymous	Exon 2 of 4	NP_579806.1	P24071-10
	FCAR	NM_133269.4		c.324G>A	p.Arg108Arg	synonymous	Exon 3 of 5	NP_579803.1	P24071-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAR	ENST00000355524.8	TSL:1 MANE Select	c.324G>A	p.Arg108Arg	synonymous	Exon 3 of 5	ENSP00000347714.3	P24071-1
	FCAR	ENST00000359272.8	TSL:1	c.288G>A	p.Arg96Arg	synonymous	Exon 2 of 4	ENSP00000352218.4	P24071-10
	FCAR	ENST00000391725.7	TSL:1	c.324G>A	p.Arg108Arg	synonymous	Exon 3 of 5	ENSP00000375605.3	P24071-2

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

African (AFR) AF: 0.132 AC: 4418 AN: 33468

American (AMR) AF: 0.478 AC: 21350 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 6945 AN: 26128

East Asian (EAS) AF: 0.291 AC: 11537 AN: 39700

South Asian (SAS) AF: 0.347 AC: 29895 AN: 86234

European-Finnish (FIN) AF: 0.343 AC: 18337 AN: 53410

Middle Eastern (MID) AF: 0.241 AC: 1387 AN: 5766

European-Non Finnish (NFE) AF: 0.277 AC: 307334 AN: 1111256

Other (OTH) AF: 0.284 AC: 17131 AN: 60366

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

African (AFR) AF: 0.141 AC: 5834 AN: 41504

American (AMR) AF: 0.410 AC: 6263 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 915 AN: 3466

East Asian (EAS) AF: 0.265 AC: 1369 AN: 5172

South Asian (SAS) AF: 0.348 AC: 1674 AN: 4812

European-Finnish (FIN) AF: 0.351 AC: 3713 AN: 10572

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.282 AC: 19160 AN: 67954

Other (OTH) AF: 0.292 AC: 618 AN: 2114

Alfa AF: 0.269 Hom.: 10125

Bravo AF: 0.257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.8
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs1865096; hg19: chr19-55396900;