19-54886824-C-T

Variant names:

• chr19-54886824-C-T
• rs12975083
• NM_002000.4:c.362-1183C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002000.4(FCAR):​c.362-1183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,116 control chromosomes in the GnomAD database, including 5,998 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 0.27 (5998 hom., cov: 32)
• Consequence: FCAR NM_002000.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.405 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAR	NM_002000.4	MANE Select	c.362-1183C>T		intron	N/A	NP_001991.1
	FCAR	NM_133272.4		c.326-1183C>T		intron	N/A	NP_579806.1
	FCAR	NM_133269.4		c.362-1183C>T		intron	N/A	NP_579803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAR	ENST00000355524.8	TSL:1 MANE Select	c.362-1183C>T		intron	N/A	ENSP00000347714.3
	FCAR	ENST00000359272.8	TSL:1	c.326-1183C>T		intron	N/A	ENSP00000352218.4
	FCAR	ENST00000391725.7	TSL:1	c.362-1183C>T		intron	N/A	ENSP00000375605.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40909 AN: 151998 Hom.: 5987 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.269 AC: 40940 AN: 152116 Hom.: 5998 Cov.: 32 AF XY: 0.279 AC XY: 20718 AN XY: 74358

African (AFR) AF: 0.170 AC: 7040 AN: 41526

American (AMR) AF: 0.413 AC: 6305 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1381 AN: 5170

South Asian (SAS) AF: 0.345 AC: 1663 AN: 4822

European-Finnish (FIN) AF: 0.352 AC: 3720 AN: 10564

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19058 AN: 67988

Other (OTH) AF: 0.294 AC: 620 AN: 2112

Alfa AF: 0.273 Hom.: 760

Bravo AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.77
PhyloP100		0.16

Splicing

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

Other links and lift over

dbSNP: rs12975083; hg19: chr19-55398235;