rs428888

Variant names:

• chr1-161548496-C-T
• rs428888
• NM_000569.8:c.244G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_000569.8(FCGR3A):​c.244G>A​(p.Asp82Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0098 (8 hom., cov: 37)
  • Exomes 𝑓: 0.00084 (36 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR3A NM_000569.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.79

Genes affected

FCGR3A (HGNC:3619): (Fc gamma receptor IIIa) This gene encodes a receptor for the Fc portion of immunoglobulin G, and it is involved in the removal of antigen-antibody complexes from the circulation, as well as other responses, including antibody dependent cellular mediated cytotoxicity and antibody dependent enhancement of virus infections. This gene (FCGR3A) is highly similar to another nearby gene (FCGR3B) located on chromosome 1. The receptor encoded by this gene is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide, whereas FCGR3B is expressed on polymorphonuclear neutrophils (PMN) where the receptor is anchored through a phosphatidylinositol (PI) linkage. Mutations in this gene are associated with immunodeficiency 20, and have been linked to susceptibility to recurrent viral infections, susceptibility to systemic lupus erythematosus, and alloimmune neonatal neutropenia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

ENSG00000289768 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.066061705).
• BP6: Variant 1-161548496-C-T is Benign according to our data. Variant chr1-161548496-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3A	NM_000569.8	c.244G>A	p.Asp82Asn	missense_variant	Exon 3 of 5	ENST00000443193.6	NP_000560.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR3A	ENST00000443193.6	c.244G>A	p.Asp82Asn	missense_variant	Exon 3 of 5	1	NM_000569.8	ENSP00000392047.2
ENSG00000289768	ENST00000699402.1	c.241G>A	p.Asp81Asn	missense_variant	Exon 3 of 4			ENSP00000514363.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1181 AN: 120458 Hom.: 8 Cov.: 37 FAILED QC

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00388

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00690

Gnomad EAS AF: 0.00540

Gnomad SAS AF: 0.00965

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0150

Gnomad NFE AF: 0.00557

Gnomad OTH AF: 0.0119

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000840 AC: 1096 AN: 1304062 Hom.: 36 Cov.: 134 AF XY: 0.000758 AC XY: 493 AN XY: 650218

Gnomad4 AFR exome AF: 0.0111

Gnomad4 AMR exome AF: 0.000440

Gnomad4 ASJ exome AF: 0.000354

Gnomad4 EAS exome AF: 0.000210

Gnomad4 SAS exome AF: 0.000530

Gnomad4 FIN exome AF: 0.000220

Gnomad4 NFE exome AF: 0.000600

Gnomad4 OTH exome AF: 0.00119

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00980 AC: 1182 AN: 120566 Hom.: 8 Cov.: 37 AF XY: 0.00991 AC XY: 587 AN XY: 59260

Gnomad4 AFR AF: 0.0174

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.00690

Gnomad4 EAS AF: 0.00542

Gnomad4 SAS AF: 0.00913

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.00557

Gnomad4 OTH AF: 0.0117

Alfa AF: 0.0636 Hom.: 1

ExAC AF: 0.00141 AC: 171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0010
DANN	Benign	0.32
DEOGEN2	Benign	0.014	.;T;T;T;.;.;.
Eigen	Benign	-2.6
Eigen_PC	Benign	-2.7
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.13	T;.;.;T;T;T;T
MetaRNN	Benign	0.066	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.065	.;N;N;N;.;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.6	.;.;N;N;.;.;N
REVEL	Benign	0.013
Sift	Benign	1.0	.;.;T;T;.;.;T
Sift4G	Benign	1.0	.;T;T;T;.;.;.
Polyphen		0.0	.;B;B;B;.;.;.
Vest4		0.11
MVP		0.18
MPC		0.13
ClinPred		0.015	T
GERP RS		-8.8
Varity_R		0.10
gMVP		0.22

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: rs428888; hg19: chr1-161518286; COSMIC: COSV63458837;