1-161626224-A-T

Variant names:

• chr1-161626224-A-T
• rs71632957
• NM_001244753.2:c.498T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001244753.2(FCGR3B):​c.498T>A​(p.Asp166Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 3 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25826675).

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.498T>A	p.Asp166Glu	missense	Exon 4 of 5	NP_001231682.2
	FCGR3B	NM_000570.5		c.498T>A	p.Asp166Glu	missense	Exon 5 of 6	NP_000561.3
	FCGR3B	NM_001271035.2		c.495T>A	p.Asp165Glu	missense	Exon 4 of 5	NP_001257964.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3B	ENST00000650385.1	MANE Select	c.498T>A	p.Asp166Glu	missense	Exon 4 of 5	ENSP00000497461.1
	ENSG00000289768	ENST00000699402.1		c.40+4831T>A		intron	N/A	ENSP00000514363.1
	FCGR3B	ENST00000367964.6	TSL:5	c.498T>A	p.Asp166Glu	missense	Exon 5 of 6	ENSP00000356941.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 247204 AF XY: 0.00

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 FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422760 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 708722

African (AFR) AF: 0.00 AC: 0 AN: 32674

American (AMR) AF: 0.00 AC: 0 AN: 44286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25618

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.00 AC: 0 AN: 84726

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52980

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5544

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078534

Other (OTH) AF: 0.00 AC: 0 AN: 58884

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.93	T
PhyloP100		2.9
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.098
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.013	D
Vest4		0.42
MutPred		0.50		Gain of methylation at K165 (P = 0.0878)
MVP		0.50
MPC		0.25
ClinPred		0.81	D
GERP RS		1.5
gMVP		0.57
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs71632957; hg19: chr1-161596014;