NM_001136219.3:c.500A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

789 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FCGR2A	NM_001136219.3	MANE Select	c.500A>G	p.His167Arg	missense	Exon 4 of 7	NP_001129691.1
FCGR2A	NM_021642.5		c.497A>G	p.His166Arg	missense	Exon 4 of 7	NP_067674.2
FCGR2A	NM_001375296.1		c.500A>G	p.His167Arg	missense	Exon 4 of 6	NP_001362225.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FCGR2A	ENST00000271450.12	TSL:1 MANE Select	c.500A>G	p.His167Arg	missense	Exon 4 of 7	ENSP00000271450.6
FCGR2A	ENST00000367972.8	TSL:1	c.497A>G	p.His166Arg	missense	Exon 4 of 7	ENSP00000356949.4
FCGR2A	ENST00000699277.1		c.500A>G	p.His167Arg	missense	Exon 4 of 6	ENSP00000514258.1

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

GnomAD2 exomes

AF:

0.476

AC:

119499

AN:

251224

AF XY:

0.471

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 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

African (AFR)

AF:

0.550

AC:

18414

AN:

33472

American (AMR)

AF:

0.513

AC:

22942

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

10534

AN:

26132

East Asian (EAS)

AF:

0.254

AC:

10083

AN:

39652

South Asian (SAS)

AF:

0.416

AC:

35849

AN:

86252

European-Finnish (FIN)

AF:

0.499

AC:

26658

AN:

53420

Middle Eastern (MID)

AF:

0.438

AC:

2522

AN:

5762

European-Non Finnish (NFE)

AF:

0.519

AC:

577270

AN:

1111878

Other (OTH)

AF:

0.503

AC:

30364

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

27245

54490

81736

108981

136226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16726

33452

50178

66904

83630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.502

AC:

76380

AN:

152046

Hom.:

19465

Cov.:

AF XY:

0.498

AC XY:

37037

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.542

AC:

22460

AN:

41452

American (AMR)

AF:

0.488

AC:

7468

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1465

AN:

3472

East Asian (EAS)

AF:

0.305

AC:

1570

AN:

5152

South Asian (SAS)

AF:

0.400

AC:

1932

AN:

4824

European-Finnish (FIN)

AF:

0.512

AC:

5408

AN:

10554

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.508

AC:

34549

AN:

67982

Other (OTH)

AF:

0.492

AC:

1038

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1962

3924

5886

7848

9810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.496

Hom.:

67949

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

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: 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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Lupus nephritis, susceptibility to

Other:1

Jul 01, 2010

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

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

Other:1

Jul 01, 2010

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

Malaria, severe, susceptibility to

Other:1

Jul 01, 2010

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.0020

(source)

DANN

Benign

0.23

DEOGEN2

Benign

0.14

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.021

MetaRNN

Benign

0.000045

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

PhyloP100

-0.46

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.053

Sift

Benign

0.17

Sift4G

Benign

0.47

Polyphen

0.0

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over