19-54889804-A-G

Variant names:

• chr19-54889804-A-G
• rs16986050
• NM_002000.4:c.805A>G

Variant summary

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

The NM_002000.4(FCAR):​c.805A>G​(p.Ser269Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,611,724 control chromosomes in the GnomAD database, including 26,796 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S269N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.20 (3676 hom., cov: 31)
  • Exomes 𝑓: 0.17 (23120 hom.)
• Consequence: FCAR NM_002000.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 31 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=0.0038774014).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 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.805A>G	p.Ser269Gly	missense	Exon 5 of 5	NP_001991.1
	FCAR	NM_133272.4		c.769A>G	p.Ser257Gly	missense	Exon 4 of 4	NP_579806.1
	FCAR	NM_133269.4		c.739A>G	p.Ser247Gly	missense	Exon 5 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.805A>G	p.Ser269Gly	missense	Exon 5 of 5	ENSP00000347714.3
	FCAR	ENST00000359272.8	TSL:1	c.769A>G	p.Ser257Gly	missense	Exon 4 of 4	ENSP00000352218.4
	FCAR	ENST00000391725.7	TSL:1	c.739A>G	p.Ser247Gly	missense	Exon 5 of 5	ENSP00000375605.3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31039 AN: 151968 Hom.: 3663 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.0574

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.145 AC: 36201 AN: 249204 AF XY: 0.142

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.0789

Gnomad ASJ exome AF: 0.0752

Gnomad EAS exome AF: 0.0180

Gnomad FIN exome AF: 0.231

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.139

GnomAD4 exome AF: 0.169 AC: 246370 AN: 1459638 Hom.: 23120 Cov.: 35 AF XY: 0.165 AC XY: 119975 AN XY: 726182

African (AFR) AF: 0.318 AC: 10647 AN: 33470

American (AMR) AF: 0.0829 AC: 3708 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0740 AC: 1935 AN: 26136

East Asian (EAS) AF: 0.0285 AC: 1132 AN: 39700

South Asian (SAS) AF: 0.0589 AC: 5081 AN: 86254

European-Finnish (FIN) AF: 0.231 AC: 11890 AN: 51432

Middle Eastern (MID) AF: 0.0774 AC: 444 AN: 5738

European-Non Finnish (NFE) AF: 0.182 AC: 201931 AN: 1111816

Other (OTH) AF: 0.159 AC: 9602 AN: 60368

GnomAD4 genome AF: 0.204 AC: 31092 AN: 152086 Hom.: 3676 Cov.: 31 AF XY: 0.202 AC XY: 15037 AN XY: 74346

African (AFR) AF: 0.312 AC: 12916 AN: 41446

American (AMR) AF: 0.133 AC: 2028 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3470

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5178

South Asian (SAS) AF: 0.0574 AC: 277 AN: 4824

European-Finnish (FIN) AF: 0.236 AC: 2498 AN: 10578

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12377 AN: 68006

Other (OTH) AF: 0.160 AC: 338 AN: 2106

Alfa AF: 0.177 Hom.: 11271

Bravo AF: 0.203

TwinsUK AF: 0.174 AC: 646

ALSPAC AF: 0.182 AC: 700

ESP6500AA AF: 0.314 AC: 1384

ESP6500EA AF: 0.177 AC: 1522

ExAC AF: 0.152 AC: 18490

Asia WGS AF: 0.0680 AC: 235 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.163

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.5
DANN	Benign	0.92
DEOGEN2	Benign	0.0094	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.027	N
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.022
Sift	Benign	0.36	T
Sift4G	Benign	0.10	T
Polyphen		0.31	B
Vest4		0.21
MPC		0.054
ClinPred		0.0084	T
GERP RS		0.85
Varity_R		0.067
gMVP		0.071
Mutation Taster		=99/1	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: rs16986050; hg19: chr19-55401170; COSMIC: COSV62029095; COSMIC: COSV62029095;