NM_001394477.1:c.454T>G

Variant names:

• chr1-161673037-T-G
• NM_001394477.1:c.454T>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001394477.1(FCGR2B):​c.454T>G​(p.Cys152Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCGR2B NM_001394477.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93
• 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)

ENSG00000234211 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.99

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.454T>G	p.Cys152Gly	missense	Exon 4 of 8	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.454T>G	p.Cys152Gly	missense	Exon 5 of 9	NP_003992.3
	FCGR2B	NM_001002275.3		c.451T>G	p.Cys151Gly	missense	Exon 5 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.454T>G	p.Cys152Gly	missense	Exon 4 of 8	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.433T>G	p.Cys145Gly	missense	Exon 3 of 7	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.454T>G	p.Cys152Gly	missense	Exon 4 of 7	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	3.8	H
PhyloP100		3.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-12	D
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.87		Loss of stability (P = 0.0172)
MVP		0.97
MPC		2.0
ClinPred		1.0	D
GERP RS		4.6
Varity_R		1.0
gMVP		0.95
Mutation Taster		=29/71	disease causing

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

hg19: chr1-161642827;