chr19-54874148-T-A

Variant names:

• chr19-54874148-T-A
• rs3816051
• NM_002000.4:c.-142T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002000.4(FCAR):​c.-142T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCAR NM_002000.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 20 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCAR	NM_002000.4	c.-142T>A		upstream_gene_variant		ENST00000355524.8	NP_001991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8	c.-142T>A		upstream_gene_variant		1	NM_002000.4	ENSP00000347714.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 740376 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 384432

African (AFR) AF: 0.00 AC: 0 AN: 18438

American (AMR) AF: 0.00 AC: 0 AN: 29638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16626

East Asian (EAS) AF: 0.00 AC: 0 AN: 34660

South Asian (SAS) AF: 0.00 AC: 0 AN: 59456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2504

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 495596

Other (OTH) AF: 0.00 AC: 0 AN: 35486

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.42
PhyloP100		-0.42
PromoterAI		-0.11	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3816051; hg19: chr19-55385604;