1-161677540-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394477.1(FCGR2B):c.920A>G(p.Gln307Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,076 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (1 hom.)
• Consequence: FCGR2B NM_001394477.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.78

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09322131).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR2B	NM_001394477.1	c.920A>G	p.Gln307Arg	missense_variant	8/8	ENST00000358671.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR2B	ENST00000358671.10	c.920A>G	p.Gln307Arg	missense_variant	8/8	1	NM_001394477.1	P4
FCGR2B	ENST00000367961.8	c.899A>G	p.Gln300Arg	missense_variant	7/7	1		A2
FCGR2B	ENST00000236937.13	c.863A>G	p.Gln288Arg	missense_variant	7/7	1		A2
FCGR2B	ENST00000480308.5	n.4167A>G		non_coding_transcript_exon_variant	6/6	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 250800 Hom.: 1 AF XY: 0.00 AC XY: 0 AN XY: 135634

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460076 Hom.: 1 Cov.: 29 AF XY: 0.00000413 AC XY: 3 AN XY: 726542

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.000334 Hom.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.920A>G (p.Q307R) alteration is located in exon 8 (coding exon 8) of the FCGR2B gene. This alteration results from a A to G substitution at nucleotide position 920, causing the glutamine (Q) at amino acid position 307 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	0.080
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	20
Dann	Benign	0.86
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.093	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.99	N;N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.058
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.024	D;D;D
Polyphen		0.19	B;P;B
Vest4		0.087
MutPred		0.25		.;.;Gain of disorder (P = 0.1885);
MVP		0.19
MPC		0.80
ClinPred		0.11	T
GERP RS		2.5
Varity_R		0.093
gMVP		0.39

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

Other links and lift over

dbSNP: rs1480128791; hg19: chr1-161647330;