19-54885501-G-A

Variant names:

• chr19-54885501-G-A
• rs11666735
• NM_002000.4:c.337G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002000.4(FCAR):​c.337G>A​(p.Asp113Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,610,560 control chromosomes in the GnomAD database, including 4,670 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.066 (364 hom., cov: 32)
  • Exomes 𝑓: 0.075 (4306 hom.)
• Consequence: FCAR NM_002000.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 22 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 (MetaRNN=0.0031760335).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAR	NM_002000.4	MANE Select	c.337G>A	p.Asp113Asn	missense	Exon 3 of 5	NP_001991.1
	FCAR	NM_133272.4		c.301G>A	p.Asp101Asn	missense	Exon 2 of 4	NP_579806.1
	FCAR	NM_133269.4		c.337G>A	p.Asp113Asn	missense	Exon 3 of 5	NP_579803.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAR	ENST00000355524.8	TSL:1 MANE Select	c.337G>A	p.Asp113Asn	missense	Exon 3 of 5	ENSP00000347714.3
	FCAR	ENST00000359272.8	TSL:1	c.301G>A	p.Asp101Asn	missense	Exon 2 of 4	ENSP00000352218.4
	FCAR	ENST00000391725.7	TSL:1	c.337G>A	p.Asp113Asn	missense	Exon 3 of 5	ENSP00000375605.3

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9971 AN: 152150 Hom.: 363 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.0698

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.0659

GnomAD2 exomes AF: 0.0689 AC: 17257 AN: 250482 AF XY: 0.0704

Gnomad AFR exome AF: 0.0468

Gnomad AMR exome AF: 0.0485

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.0371

Gnomad FIN exome AF: 0.0605

Gnomad NFE exome AF: 0.0793

Gnomad OTH exome AF: 0.0712

GnomAD4 exome AF: 0.0745 AC: 108666 AN: 1458292 Hom.: 4306 Cov.: 32 AF XY: 0.0749 AC XY: 54332 AN XY: 725548

African (AFR) AF: 0.0460 AC: 1540 AN: 33442

American (AMR) AF: 0.0485 AC: 2167 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3173 AN: 26092

East Asian (EAS) AF: 0.0341 AC: 1352 AN: 39682

South Asian (SAS) AF: 0.0707 AC: 6093 AN: 86192

European-Finnish (FIN) AF: 0.0647 AC: 3456 AN: 53410

Middle Eastern (MID) AF: 0.0588 AC: 339 AN: 5766

European-Non Finnish (NFE) AF: 0.0775 AC: 85933 AN: 1108698

Other (OTH) AF: 0.0765 AC: 4613 AN: 60298

GnomAD4 genome AF: 0.0655 AC: 9976 AN: 152268 Hom.: 364 Cov.: 32 AF XY: 0.0649 AC XY: 4835 AN XY: 74456

African (AFR) AF: 0.0466 AC: 1937 AN: 41546

American (AMR) AF: 0.0544 AC: 832 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3468

East Asian (EAS) AF: 0.0403 AC: 209 AN: 5188

South Asian (SAS) AF: 0.0705 AC: 340 AN: 4826

European-Finnish (FIN) AF: 0.0588 AC: 624 AN: 10610

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0794 AC: 5400 AN: 68024

Other (OTH) AF: 0.0652 AC: 138 AN: 2116

Alfa AF: 0.0764 Hom.: 1886

Bravo AF: 0.0642

TwinsUK AF: 0.0825 AC: 306

ALSPAC AF: 0.0669 AC: 258

ESP6500AA AF: 0.0438 AC: 193

ESP6500EA AF: 0.0824 AC: 709

ExAC AF: 0.0691 AC: 8395

Asia WGS AF: 0.0490 AC: 169 AN: 3478

EpiCase AF: 0.0832

EpiControl AF: 0.0826

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.89
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.029
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.020
Sift	Benign	0.60	T
Sift4G	Benign	0.32	T
Polyphen		0.0080	B
Vest4		0.15
MPC		0.056
ClinPred		0.0059	T
GERP RS		-0.13
Varity_R		0.25
gMVP		0.14
Mutation Taster		=99/1	polymorphism (auto)

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

dbSNP: rs11666735; hg19: chr19-55396913; COSMIC: COSV62028915;