Genetic Variant FCGR2B:p.Tyr205Phe (chr1-161673197-A-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001394477.1(FCGR2B):c.614A>T(p.Tyr205Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,604,836 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 17 hom. )

Consequence

FCGR2B
NM_001394477.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.894

Variant links:

Genes affected

FCGR2B (HGNC:3618): (Fc gamma receptor IIb) The protein encoded by this gene is a low affinity receptor for the Fc region of immunoglobulin gamma complexes. The encoded protein is involved in the phagocytosis of immune complexes and in the regulation of antibody production by B-cells. Variations in this gene may increase susceptibilty to systemic lupus erythematosus (SLE). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

FCGR2B links:

ENSG00000234211 (HGNC:):

ENSG00000234211 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0054632127).

BP6

Variant 1-161673197-A-T is Benign according to our data. Variant chr1-161673197-A-T is described in ClinVar as [Benign]. Clinvar id is 3387964.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-161673197-A-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00452 (679/150128) while in subpopulation AMR AF= 0.0172 (256/14854). AF 95% confidence interval is 0.0155. There are 0 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR2B	NM_001394477.1 link	c.614A>T	p.Tyr205Phe	missense_variant	Exon 4 of 8	ENST00000358671.10	NP_001381406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR2B	ENST00000358671.10 link	c.614A>T	p.Tyr205Phe	missense_variant	Exon 4 of 8	1	NM_001394477.1	ENSP00000351497.5		P31994-1

Frequencies

GnomAD3 genomes

AF:

0.00453

AC:

679

AN:

150016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00585

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.0137

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00120

Gnomad OTH

AF:

0.00243

GnomAD3 exomes

AF:

0.00236

AC:

582

AN:

246368

Hom.:

AF XY:

0.00239

AC XY:

319

AN XY:

133196

show subpopulations

Gnomad AFR exome

AF:

0.00352

Gnomad AMR exome

AF:

0.00514

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00721

Gnomad SAS exome

AF:

0.00410

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000743

Gnomad OTH exome

AF:

0.00250

GnomAD4 exome

AF:

0.00171

AC:

2481

AN:

1454708

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1335

AN XY:

723322

show subpopulations

Gnomad4 AFR exome

AF:

0.00478

Gnomad4 AMR exome

AF:

0.00703

Gnomad4 ASJ exome

AF:

0.000116

Gnomad4 EAS exome

AF:

0.0104

Gnomad4 SAS exome

AF:

0.00543

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000842

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.00452

AC:

679

AN:

150128

Hom.:

Cov.:

AF XY:

0.00514

AC XY:

377

AN XY:

73300

show subpopulations

Gnomad4 AFR

AF:

0.00583

Gnomad4 AMR

AF:

0.0172

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.0137

Gnomad4 SAS

AF:

0.00623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00120

Gnomad4 OTH

AF:

0.00241

Alfa

AF:

0.00187

Hom.:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00185

AC:

224

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FCGR2B: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.6

DANN

Benign

0.56

DEOGEN2

Benign

0.092

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.12

T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;.;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.075

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.15

MVP

0.072

MPC

0.69

ClinPred

0.0069

GERP RS

1.2

Varity_R

0.44

gMVP

0.17

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