chr1-161544752-A-C

Position:

chr1-161544752-A-C

Variant summary

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

The NM_000569.8(FCGR3A):c.526T>G(p.Phe176Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,544,462 control chromosomes in the GnomAD database, including 87,029 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 Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.33 ( 8307 hom., cov: 30)

Exomes 𝑓: 0.32 ( 78722 hom. )

Consequence

FCGR3A
NM_000569.8 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.375

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:

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=0.004077375).

BP6

Variant 1-161544752-A-C is Benign according to our data. Variant chr1-161544752-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 225994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR3A	NM_000569.8 linkuse as main transcript	c.526T>G	p.Phe176Val	missense_variant	4/5	ENST00000443193.6	NP_000560.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR3A	ENST00000443193.6 linkuse as main transcript	c.526T>G	p.Phe176Val	missense_variant	4/5	1	NM_000569.8	ENSP00000392047	P4

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

49910

AN:

151126

Hom.:

8283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.334

Gnomad AMI

AF:

0.379

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.442

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.343

GnomAD3 exomes

AF:

0.325

AC:

80158

AN:

246638

Hom.:

13615

AF XY:

0.330

AC XY:

43997

AN XY:

133362

show subpopulations

Gnomad AFR exome

AF:

0.329

Gnomad AMR exome

AF:

0.239

Gnomad ASJ exome

AF:

0.416

Gnomad EAS exome

AF:

0.337

Gnomad SAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.318

AC:

443648

AN:

1393218

Hom.:

78722

Cov.:

AF XY:

0.321

AC XY:

223512

AN XY:

695626

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.246

Gnomad4 ASJ exome

AF:

0.414

Gnomad4 EAS exome

AF:

0.301

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.271

Gnomad4 NFE exome

AF:

0.319

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.330

AC:

49964

AN:

151244

Hom.:

8307

Cov.:

AF XY:

0.329

AC XY:

24287

AN XY:

73876

show subpopulations

Gnomad4 AFR

AF:

0.335

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.408

Gnomad4 EAS

AF:

0.327

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.342

Gnomad4 OTH

AF:

0.344

Alfa

AF:

0.319

Hom.:

3321

Bravo

AF:

0.334

ESP6500AA

AF:

0.261

AC:

1150

ESP6500EA

AF:

0.280

AC:

2412

ExAC

AF:

0.331

AC:

40146

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -
Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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: Polymorphism that reportedly influences the strength of the antibody-dependent cellular cytotoxicity responses by NK cells. Associated with progression to end stage renal disease in lupus patients (17076550). NOT associated with suscepitibility to tuberculosis in Morrocan population (PMID 20439102) -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.12

DANN

Benign

0.38

DEOGEN2

Benign

0.015

.;T;T;T;.;.

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.073

T;.;.;T;T;T

MetaRNN

Benign

0.0041

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.16

.;N;N;N;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

1.7

N;.;N;N;.;.

REVEL

Benign

0.064

Sift

Benign

1.0

T;.;T;T;.;.

Sift4G

Benign

0.13

.;T;T;T;.;.

Polyphen

0.0

.;B;B;B;.;.

Vest4

0.070

MPC

0.17

ClinPred

0.0061

GERP RS

-0.10

Varity_R

0.19

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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