Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000358671.10(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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 17 hom. )

Consequence

FCGR2B
ENST00000358671.10 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.894

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

FCGR2B links:

ENSG00000234211 (HGNC:):

ENSG00000234211 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3387964.Status of the report is criteria_provided_single_submitter, 1 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 17 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000358671.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FCGR2B	NM_001394477.1	MANE Select	c.614A>T	p.Tyr205Phe	missense	Exon 4 of 8	NP_001381406.1
FCGR2B	NM_004001.5		c.614A>T	p.Tyr205Phe	missense	Exon 5 of 9	NP_003992.3
FCGR2B	NM_001002275.3		c.611A>T	p.Tyr204Phe	missense	Exon 5 of 9	NP_001002275.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FCGR2B	ENST00000358671.10	TSL:1 MANE Select	c.614A>T	p.Tyr205Phe	missense	Exon 4 of 8	ENSP00000351497.5
FCGR2B	ENST00000367961.8	TSL:1	c.593A>T	p.Tyr198Phe	missense	Exon 3 of 7	ENSP00000356938.4
FCGR2B	ENST00000236937.13	TSL:1	c.614A>T	p.Tyr205Phe	missense	Exon 4 of 7	ENSP00000236937.9

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

GnomAD2 exomes

AF:

0.00236

AC:

582

AN:

246368

AF XY:

0.00239

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 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

African (AFR)

AF:

0.00478

AC:

158

AN:

33058

American (AMR)

AF:

0.00703

AC:

309

AN:

43954

Ashkenazi Jewish (ASJ)

AF:

0.000116

AC:

AN:

25946

East Asian (EAS)

AF:

0.0104

AC:

410

AN:

39516

South Asian (SAS)

AF:

0.00543

AC:

463

AN:

85234

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53234

Middle Eastern (MID)

AF:

0.00440

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.000842

AC:

933

AN:

1108018

Other (OTH)

AF:

0.00280

AC:

168

AN:

60072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

159

239

318

398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.00452

AC:

679

AN:

150128

Hom.:

Cov.:

AF XY:

0.00514

AC XY:

377

AN XY:

73300

show subpopulations

African (AFR)

AF:

0.00583

AC:

237

AN:

40636

American (AMR)

AF:

0.0172

AC:

256

AN:

14854

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3458

East Asian (EAS)

AF:

0.0137

AC:

AN:

5096

South Asian (SAS)

AF:

0.00623

AC:

AN:

4654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00120

AC:

AN:

67680

Other (OTH)

AF:

0.00241

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00187

Hom.:

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00185

AC:

224

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.6

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.092

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.12

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

PhyloP100

0.89

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

REVEL

Benign

0.075

Sift

Benign

0.30

Sift4G

Benign

0.28

Polyphen

0.0010

Vest4

0.15

MVP

0.072

MPC

0.69

ClinPred

0.0069

GERP RS

1.2

Varity_R

0.44

gMVP

0.17

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1050499

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over