Variant chr1-161677358-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394477.1(FCGR2B):c.848A>G(p.Lys283Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000516 in 1,613,500 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 1 hom. )

Consequence

FCGR2B
NM_001394477.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.701

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014487654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR2B	NM_001394477.1 linkuse as main transcript	c.848A>G	p.Lys283Arg	missense_variant	7/8	ENST00000358671.10	NP_001381406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR2B	ENST00000358671.10 linkuse as main transcript	c.848A>G	p.Lys283Arg	missense_variant	7/8	1	NM_001394477.1	ENSP00000351497	P4	P31994-1
FCGR2B	ENST00000367961.8 linkuse as main transcript	c.827A>G	p.Lys276Arg	missense_variant	6/7	1		ENSP00000356938	A2	P31994-3
FCGR2B	ENST00000236937.13 linkuse as main transcript	c.791A>G	p.Lys264Arg	missense_variant	6/7	1		ENSP00000236937	A2	P31994-2
FCGR2B	ENST00000480308.5 linkuse as main transcript	n.4095A>G		non_coding_transcript_exon_variant	5/6	1

Frequencies

GnomAD3 genomes

AF:

0.000395

AC:

AN:

151872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000287

AC:

AN:

251012

Hom.:

AF XY:

0.000310

AC XY:

AN XY:

135678

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000349

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000458

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000529

AC:

773

AN:

1461510

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

361

AN XY:

727062

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000314

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.000625

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000395

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000472

Gnomad4 NFE

AF:

0.000589

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000460

Hom.:

Bravo

AF:

0.000389

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

The c.848A>G (p.K283R) alteration is located in exon 7 (coding exon 7) of the FCGR2B gene. This alteration results from a A to G substitution at nucleotide position 848, causing the lysine (K) at amino acid position 283 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.047

.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.14

.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.022

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.021

B;B;B

Vest4

0.096

MVP

0.12

MPC

0.74

ClinPred

0.010

GERP RS

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.20

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