chr19-54889804-A-G

Position:

• chr19-54889804-A-G

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 0.20 (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

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]

FCAR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCAR	NM_002000.4	c.805A>G	p.Ser269Gly	missense_variant	5/5	ENST00000355524.8	NP_001991.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8	c.805A>G	p.Ser269Gly	missense_variant	5/5	1	NM_002000.4	ENSP00000347714.3

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

GnomAD3 exomes AF: 0.145 AC: 36201 AN: 249204 Hom.: 3413 AF XY: 0.142 AC XY: 19090 AN XY: 134874

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 SAS exome AF: 0.0589

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

Gnomad4 AFR exome AF: 0.318

Gnomad4 AMR exome AF: 0.0829

Gnomad4 ASJ exome AF: 0.0740

Gnomad4 EAS exome AF: 0.0285

Gnomad4 SAS exome AF: 0.0589

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.159

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

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.0574

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.160

Alfa AF: 0.167 Hom.: 4886

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 v4.3

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;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	.;L;.;.;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.99	N;N;N;N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.36	T;D;D;T;D;D;D
Sift4G	Benign	0.10	T;T;T;T;D;T;T
Polyphen		0.31, 0.053	.;B;.;B;.;.;.
Vest4		0.21
MPC		0.054
ClinPred		0.0084	T
GERP RS		0.85
Varity_R		0.067
gMVP		0.071

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

Publications

LitVar

Other links and lift over

dbSNP: rs16986050; hg19: chr19-55401170; COSMIC: COSV62029095; COSMIC: COSV62029095;