rs2304225

Positions:

• chr19-54874506-C-G
• chr19-54874506-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002000.4(FCAR):​c.34+183C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0521 in 152,192 control chromosomes in the GnomAD database, including 319 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 0.052 (319 hom., cov: 32)
• Consequence: FCAR NM_002000.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.360

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCAR	NM_002000.4	c.34+183C>G		intron_variant		ENST00000355524.8	NP_001991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8	c.34+183C>G		intron_variant		1	NM_002000.4	ENSP00000347714	P2

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7919 AN: 152074 Hom.: 319 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.0559

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0521 AC: 7922 AN: 152192 Hom.: 319 Cov.: 32 AF XY: 0.0518 AC XY: 3853 AN XY: 74400

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.0790

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.0398

Gnomad4 NFE AF: 0.0644

Gnomad4 OTH AF: 0.0577

Alfa AF: 0.0372 Hom.: 34

Bravo AF: 0.0526

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.34

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

Other links and lift over

dbSNP: rs2304225; hg19: chr19-55385962;