chr1-161548546-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000569.8(FCGR3A):c.194G>A(p.Ser65Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,149,004 control chromosomes in the GnomAD database, including 15 homozygotes. 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 ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 0 hom., cov: 35)

Exomes 𝑓: 0.11 ( 15 hom. )

Failed GnomAD Quality Control

Consequence

FCGR3A
NM_000569.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.24

Variant links:

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]

FCGR3A links:

ENSG00000289768 (HGNC:):

ENSG00000289768 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014047027).

BP6

Variant 1-161548546-C-T is Benign according to our data. Variant chr1-161548546-C-T is described in ClinVar as [Benign]. Clinvar id is 156330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161548546-C-T is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3A	NM_000569.8 link	c.194G>A	p.Ser65Asn	missense_variant	Exon 3 of 5	ENST00000443193.6	NP_000560.7	P08637

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR3A	ENST00000443193.6 link	c.194G>A	p.Ser65Asn	missense_variant	Exon 3 of 5	1	NM_000569.8	ENSP00000392047.2		P08637
ENSG00000289768	ENST00000699402.1 link	c.191G>A	p.Ser64Asn	missense_variant	Exon 3 of 4			ENSP00000514363.1		A0A8V8TN80

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

32471

AN:

127910

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.187

Gnomad EAS

AF:

0.422

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.267

Gnomad MID

AF:

0.211

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.247

GnomAD3 exomes

AF:

0.0964

AC:

17995

AN:

186676

Hom.:

AF XY:

0.0883

AC XY:

9001

AN XY:

101962

show subpopulations

Gnomad AFR exome

AF:

0.0798

Gnomad AMR exome

AF:

0.187

Gnomad ASJ exome

AF:

0.0438

Gnomad EAS exome

AF:

0.260

Gnomad SAS exome

AF:

0.0893

Gnomad FIN exome

AF:

0.0799

Gnomad NFE exome

AF:

0.0636

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.111

AC:

127438

AN:

1149004

Hom.:

Cov.:

AF XY:

0.117

AC XY:

67072

AN XY:

572096

show subpopulations

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.246

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.385

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.0817

Gnomad4 OTH exome

AF:

0.136

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.254

AC:

32490

AN:

127974

Hom.:

Cov.:

AF XY:

0.257

AC XY:

16109

AN XY:

62600

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.321

Gnomad4 ASJ

AF:

0.187

Gnomad4 EAS

AF:

0.422

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.267

Gnomad4 NFE

AF:

0.248

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.171

Hom.:

ExAC

AF:

0.0958

AC:

11635

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.017

DANN

Benign

0.60

DEOGEN2

Benign

0.030

.;T;T;T;.;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.28

T;.;.;T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.85

.;L;L;L;.;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.42

.;.;N;N;.;.;N

REVEL

Benign

0.028

Sift

Benign

0.35

.;.;T;T;.;.;T

Sift4G

Benign

0.38

.;T;T;T;.;.;.

Polyphen

0.079

.;B;B;B;.;.;.

Vest4

0.037

MPC

0.12

ClinPred

0.018

GERP RS

-8.9

Varity_R

0.12

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over