chr19-54888208-C-T

Variant names:

• chr19-54888208-C-T
• NM_002000.4:c.563C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002000.4(FCAR):​c.563C>T​(p.Ser188Leu) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FCAR NM_002000.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.520
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3998903).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAR	NM_002000.4	MANE Select	c.563C>T	p.Ser188Leu	missense	Exon 4 of 5	NP_001991.1	P24071-1
	FCAR	NM_133272.4		c.527C>T	p.Ser176Leu	missense	Exon 3 of 4	NP_579806.1	P24071-10
	FCAR	NM_133269.4		c.563C>T	p.Ser188Leu	missense	Exon 4 of 5	NP_579803.1	P24071-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAR	ENST00000355524.8	TSL:1 MANE Select	c.563C>T	p.Ser188Leu	missense	Exon 4 of 5	ENSP00000347714.3	P24071-1
	FCAR	ENST00000359272.8	TSL:1	c.527C>T	p.Ser176Leu	missense	Exon 3 of 4	ENSP00000352218.4	P24071-10
	FCAR	ENST00000391725.7	TSL:1	c.563C>T	p.Ser188Leu	missense	Exon 4 of 5	ENSP00000375605.3	P24071-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.0068	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.52
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.050
Sift	Benign	0.038	D
Sift4G	Benign	0.16	T
Polyphen		0.90	P
Vest4		0.21
MutPred		0.58		Loss of glycosylation at S188 (P = 0.0168)
MVP		0.34
MPC		0.33
ClinPred		0.76	D
GERP RS		-0.83
Varity_R		0.19
gMVP		0.29
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr19-55399575;