19-54881299-C-T

Variant names:

• chr19-54881299-C-T
• rs7259347
• NM_002000.4:c.71-3936C>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.71-3936C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 151,926 control chromosomes in the GnomAD database, including 47,269 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 0.78 (47269 hom., cov: 30)
• Consequence: FCAR NM_002000.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCAR	NM_002000.4	c.71-3936C>T		intron_variant	Intron 2 of 4	ENST00000355524.8	NP_001991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8	c.71-3936C>T		intron_variant	Intron 2 of 4	1	NM_002000.4	ENSP00000347714.3

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118874 AN: 151808 Hom.: 47247 Cov.: 30

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.840

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.783 AC: 118946 AN: 151926 Hom.: 47269 Cov.: 30 AF XY: 0.786 AC XY: 58370 AN XY: 74254

African (AFR) AF: 0.645 AC: 26704 AN: 41384

American (AMR) AF: 0.841 AC: 12831 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2926 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5127 AN: 5144

South Asian (SAS) AF: 0.769 AC: 3708 AN: 4820

European-Finnish (FIN) AF: 0.853 AC: 9019 AN: 10568

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.826 AC: 56145 AN: 67958

Other (OTH) AF: 0.798 AC: 1686 AN: 2114

Alfa AF: 0.816 Hom.: 37602

Bravo AF: 0.781

Asia WGS AF: 0.880 AC: 3060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.45
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7259347; hg19: chr19-55392755;