NM_002000.4:c.-142T>C

Variant names:

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

Variant summary

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

The NM_002000.4(FCAR):​c.-142T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 890,642 control chromosomes in the GnomAD database, including 106,159 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 0.45 (15695 hom., cov: 32)
  • Exomes 𝑓: 0.49 (90464 hom.)
• Consequence: FCAR NM_002000.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCAR	NM_002000.4	c.-142T>C		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>C		upstream_gene_variant		1	NM_002000.4	ENSP00000347714.3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68142 AN: 151938 Hom.: 15685 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.491 AC: 362902 AN: 738584 Hom.: 90464 AF XY: 0.497 AC XY: 190682 AN XY: 383546

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.465

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.389

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.499

GnomAD4 genome AF: 0.448 AC: 68189 AN: 152058 Hom.: 15695 Cov.: 32 AF XY: 0.452 AC XY: 33612 AN XY: 74320

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.478

Alfa AF: 0.485 Hom.: 25901

Bravo AF: 0.439

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3816051; hg19: chr19-55385604; COSMIC: COSV62032303;