rs11666735

Positions:

• chr19-54885501-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 (MetaRNN=0.0031760335).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCAR	NM_002000.4	c.337G>A	p.Asp113Asn	missense_variant	3/5	ENST00000355524.8	NP_001991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8	c.337G>A	p.Asp113Asn	missense_variant	3/5	1	NM_002000.4	ENSP00000347714	P2

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

GnomAD3 exomes AF: 0.0689 AC: 17257 AN: 250482 Hom.: 646 AF XY: 0.0704 AC XY: 9534 AN XY: 135488

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 SAS exome AF: 0.0715

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

Gnomad4 AFR exome AF: 0.0460

Gnomad4 AMR exome AF: 0.0485

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0341

Gnomad4 SAS exome AF: 0.0707

Gnomad4 FIN exome AF: 0.0647

Gnomad4 NFE exome AF: 0.0775

Gnomad4 OTH exome AF: 0.0765

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

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.0544

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0403

Gnomad4 SAS AF: 0.0705

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.0794

Gnomad4 OTH AF: 0.0652

Alfa AF: 0.0784 Hom.: 934

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 v4.3

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;T;T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	.;M;M;M;M;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N;.;N;D;D;N;N;D
REVEL	Benign	0.020
Sift	Benign	0.60	T;.;T;T;T;T;T;T
Sift4G	Benign	0.32	T;T;T;T;T;T;T;T
Polyphen		0.0080, 0.12, 0.030	.;B;B;.;B;.;.;.
Vest4		0.15
MPC		0.056
ClinPred		0.0059	T
GERP RS		-0.13
Varity_R		0.25
gMVP		0.14

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

Publications

LitVar

Other links and lift over

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