1-161677510-A-T

Variant names:

• chr1-161677510-A-T
• rs2102683328
• NM_001394477.1:c.890A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394477.1(FCGR2B):​c.890A>T​(p.His297Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. H297R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCGR2B NM_001394477.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33619452).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2B	NM_001394477.1	MANE Select	c.890A>T	p.His297Leu	missense	Exon 8 of 8	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.890A>T	p.His297Leu	missense	Exon 9 of 9	NP_003992.3
	FCGR2B	NM_001002275.3		c.887A>T	p.His296Leu	missense	Exon 9 of 9	NP_001002275.1	P31994-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2B	ENST00000358671.10	TSL:1 MANE Select	c.890A>T	p.His297Leu	missense	Exon 8 of 8	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.869A>T	p.His290Leu	missense	Exon 7 of 7	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.833A>T	p.His278Leu	missense	Exon 7 of 7	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.15
Eigen_PC	Benign	-0.0066
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.7
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.21		Loss of phosphorylation at Y292 (P = 0.1675)
MVP		0.46
MPC		1.9
ClinPred		0.95	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.41
gMVP		0.52
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs2102683328; hg19: chr1-161647300;