1-161509955-A-G

Position:

chr1-161509955-A-G

Variant summary

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

The NM_001136219.3(FCGR2A):c.500A>G(p.His167Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,613,712 control chromosomes in the GnomAD database, including 206,994 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19465 hom., cov: 32)

Exomes 𝑓: 0.50 ( 187529 hom. )

Consequence

FCGR2A
NM_001136219.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:3

Conservation

PhyloP100: -0.458

Variant links:

Genes affected

FCGR2A (HGNC:3616): (Fc gamma receptor IIa) This gene encodes one member of a family of immunoglobulin Fc receptor genes found on the surface of many immune response cells. The protein encoded by this gene is a cell surface receptor found on phagocytic cells such as macrophages and neutrophils, and is involved in the process of phagocytosis and clearing of immune complexes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2008]

FCGR2A links:

FCGR2A (HGNC:):

FCGR2A 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=4.473957E-5).

BP6

Variant 1-161509955-A-G is Benign according to our data. Variant chr1-161509955-A-G is described in ClinVar as [Benign]. Clinvar id is 14823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR2A	NM_001136219.3 linkuse as main transcript	c.500A>G	p.His167Arg	missense_variant	4/7	ENST00000271450.12	NP_001129691.1	P12318-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR2A	ENST00000271450.12 linkuse as main transcript	c.500A>G	p.His167Arg	missense_variant	4/7	1	NM_001136219.3	ENSP00000271450.6		P12318-1

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76314

AN:

151928

Hom.:

19447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.542

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.492

GnomAD3 exomes

AF:

0.476

AC:

119499

AN:

251224

Hom.:

29024

AF XY:

0.471

AC XY:

63904

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.547

Gnomad AMR exome

AF:

0.517

Gnomad ASJ exome

AF:

0.405

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.417

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.497

Gnomad OTH exome

AF:

0.474

GnomAD4 exome

AF:

0.503

AC:

734636

AN:

1461666

Hom.:

187529

Cov.:

106

AF XY:

0.498

AC XY:

361788

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.550

Gnomad4 AMR exome

AF:

0.513

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.254

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.499

Gnomad4 NFE exome

AF:

0.519

Gnomad4 OTH exome

AF:

0.503

GnomAD4 genome

AF:

0.502

AC:

76380

AN:

152046

Hom.:

19465

Cov.:

AF XY:

0.498

AC XY:

37037

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.542

Gnomad4 AMR

AF:

0.488

Gnomad4 ASJ

AF:

0.422

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.400

Gnomad4 FIN

AF:

0.512

Gnomad4 NFE

AF:

0.508

Gnomad4 OTH

AF:

0.492

Alfa

AF:

0.490

Hom.:

43540

Bravo

AF:

0.508

TwinsUK

AF:

0.530

AC:

1964

ALSPAC

AF:

0.533

AC:

2054

ESP6500AA

AF:

0.558

AC:

2460

ESP6500EA

AF:

0.517

AC:

4446

ExAC

AF:

0.479

AC:

58150

Asia WGS

AF:

0.383

AC:

1334

AN:

3478

EpiCase

AF:

0.485

EpiControl

AF:

0.480

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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: Variant reported as a risk factor for lupus nephritis, severe malaria, p. aeurginosa infection, and reduced risk for ulcerative colitis - questionable and unrelated to patient disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Lupus nephritis, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2010

- -

Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2010

- -

Malaria, severe, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0020

DANN

Benign

0.23

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.021

T;T

MetaRNN

Benign

0.000045

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

.;L

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.053

Sift

Benign

0.17

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0

B;B

Vest4

0.031

MPC

0.26

ClinPred

0.026

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.47

gMVP

0.58

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

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