NM_002000.4:c.75C>A

Variant names:

• chr19-54885239-C-A
• rs1024760327
• NM_002000.4:c.75C>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.75C>A​(p.Asp25Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000891 in 1,459,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: FCAR NM_002000.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.90
• 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: 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 (MetaRNN=0.061074644).

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.75C>A	p.Asp25Glu	missense	Exon 3 of 5	NP_001991.1	P24071-1
	FCAR	NM_133272.4		c.39C>A	p.Asp13Glu	missense	Exon 2 of 4	NP_579806.1	P24071-10
	FCAR	NM_133269.4		c.75C>A	p.Asp25Glu	missense	Exon 3 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.75C>A	p.Asp25Glu	missense	Exon 3 of 5	ENSP00000347714.3	P24071-1
	FCAR	ENST00000359272.8	TSL:1	c.39C>A	p.Asp13Glu	missense	Exon 2 of 4	ENSP00000352218.4	P24071-10
	FCAR	ENST00000391725.7	TSL:1	c.75C>A	p.Asp25Glu	missense	Exon 3 of 5	ENSP00000375605.3	P24071-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000891 AC: 13 AN: 1459090 Hom.: 0 Cov.: 33 AF XY: 0.00000827 AC XY: 6 AN XY: 725372

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.00 AC: 0 AN: 44586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1109798

Other (OTH) AF: 0.00 AC: 0 AN: 60270

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000370 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.14
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.040
DANN	Benign	0.16
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.050	N
PhyloP100		-1.9
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.012
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.086
MutPred		0.36		Gain of solvent accessibility (P = 0.0638)
MVP		0.13
MPC		0.054
ClinPred		0.039	T
GERP RS		-1.4
Varity_R		0.11
gMVP		0.089
Mutation Taster		=96/4	polymorphism

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: rs1024760327; hg19: chr19-55396651;