Genetic Variant NM_001394477.1:c.911C>G (chr1-161677531-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001394477.1(FCGR2B):c.911C>G(p.Pro304Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P304L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FCGR2B
NM_001394477.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.343

Publications

0 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: Orphanet, Labcorp Genetics (formerly Invitae)

FCGR2B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04181528).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394477.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCGR2B	NM_001394477.1	MANE Select	c.911C>G	p.Pro304Arg	missense	Exon 8 of 8	NP_001381406.1	P31994-1
FCGR2B	NM_004001.5		c.911C>G	p.Pro304Arg	missense	Exon 9 of 9	NP_003992.3
FCGR2B	NM_001002275.3		c.908C>G	p.Pro303Arg	missense	Exon 9 of 9	NP_001002275.1	P31994-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCGR2B	ENST00000358671.10	TSL:1 MANE Select	c.911C>G	p.Pro304Arg	missense	Exon 8 of 8	ENSP00000351497.5	P31994-1
FCGR2B	ENST00000367961.8	TSL:1	c.890C>G	p.Pro297Arg	missense	Exon 7 of 7	ENSP00000356938.4	P31994-3
FCGR2B	ENST00000236937.13	TSL:1	c.854C>G	p.Pro285Arg	missense	Exon 7 of 7	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726876

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33442

American (AMR)

AF:

0.00

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111230

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.056

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.60

M_CAP

Benign

0.014

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

-0.34

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

REVEL

Benign

0.047

Sift

Benign

0.067

Sift4G

Benign

0.13

Polyphen

0.090

Vest4

0.17

MutPred

0.34

Loss of disorder (P = 0.1777)

MVP

0.12

MPC

1.4

ClinPred

0.30

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.044

gMVP

0.096

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over