chr1-161629807-C-A

Variant names:

• chr1-161629807-C-A
• rs370893367
• NM_001244753.2:c.290G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001244753.2(FCGR3B):​c.290G>T​(p.Ser97Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. S97N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 10)
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59
• Publications: 1 publications found

Genes affected

FCGR3B (HGNC:3620): (Fc gamma receptor IIIb) The protein encoded by this gene is a low affinity receptor for the Fc region of gamma immunoglobulins (IgG). The encoded protein acts as a monomer and can bind either monomeric or aggregated IgG. This gene may function to capture immune complexes in the peripheral circulation. Several transcript variants encoding different isoforms have been found for this gene. A highly-similar gene encoding a related protein is also found on chromosome 1. [provided by RefSeq, Aug 2012]

FCGR3B Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289768 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244753.2. 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
	FCGR3B	NM_001244753.2	MANE Select	c.290G>T	p.Ser97Ile	missense	Exon 3 of 5	NP_001231682.2	A0A3B3ISU3
	FCGR3B	NM_000570.5		c.290G>T	p.Ser97Ile	missense	Exon 4 of 6	NP_000561.3	O75015
	FCGR3B	NM_001271035.2		c.287G>T	p.Ser96Ile	missense	Exon 3 of 5	NP_001257964.2	H0Y4U3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3B	ENST00000650385.1	MANE Select	c.290G>T	p.Ser97Ile	missense	Exon 3 of 5	ENSP00000497461.1	A0A3B3ISU3
	ENSG00000289768	ENST00000699402.1		c.40+1248G>T		intron	N/A	ENSP00000514363.1	A0A8V8TN80
	FCGR3B	ENST00000367964.6	TSL:5	c.290G>T	p.Ser97Ile	missense	Exon 4 of 6	ENSP00000356941.2	O75015

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 10

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000234 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.79	T
PhyloP100		3.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.66
MVP		0.69
MPC		3.4
ClinPred		1.0	D
GERP RS		2.8
gMVP		0.77
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs370893367; hg19: chr1-161599597;