NM_001244753.2:c.108C>G

Variant names:

• chr1-161629989-G-C
• rs200688856
• NM_001244753.2:c.108C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001244753.2(FCGR3B):​c.108C>G​(p.Ser36Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 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: 𝑓 0.00071 (1 hom., cov: 17)
  • Exomes 𝑓: 0.0039 (2339 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 21 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0085681975).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3B	NM_001244753.2	MANE Select	c.108C>G	p.Ser36Arg	missense	Exon 3 of 5	NP_001231682.2
	FCGR3B	NM_000570.5		c.108C>G	p.Ser36Arg	missense	Exon 4 of 6	NP_000561.3
	FCGR3B	NM_001271035.2		c.105C>G	p.Ser35Arg	missense	Exon 3 of 5	NP_001257964.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3B	ENST00000650385.1	MANE Select	c.108C>G	p.Ser36Arg	missense	Exon 3 of 5	ENSP00000497461.1
	ENSG00000289768	ENST00000699402.1		c.40+1066C>G		intron	N/A	ENSP00000514363.1
	FCGR3B	ENST00000367964.6	TSL:5	c.108C>G	p.Ser36Arg	missense	Exon 4 of 6	ENSP00000356941.2

Frequencies

GnomAD3 genomes AF: 0.000715 AC: 77 AN: 107672 Hom.: 1 Cov.: 17

Gnomad AFR AF: 0.000518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000943

Gnomad ASJ AF: 0.000345

Gnomad EAS AF: 0.00253

Gnomad SAS AF: 0.00142

Gnomad FIN AF: 0.000128

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000775

Gnomad OTH AF: 0.000686

GnomAD2 exomes AF: 0.0115 AC: 2393 AN: 208406 AF XY: 0.0114

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.00311

Gnomad EAS exome AF: 0.0566

Gnomad FIN exome AF: 0.00140

Gnomad NFE exome AF: 0.00672

Gnomad OTH exome AF: 0.0119

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00388 AC: 4861 AN: 1252378 Hom.: 2339 Cov.: 33 AF XY: 0.00434 AC XY: 2701 AN XY: 622174

African (AFR) AF: 0.00552 AC: 143 AN: 25888

American (AMR) AF: 0.0155 AC: 530 AN: 34116

Ashkenazi Jewish (ASJ) AF: 0.00206 AC: 49 AN: 23778

East Asian (EAS) AF: 0.0271 AC: 670 AN: 24680

South Asian (SAS) AF: 0.0152 AC: 1033 AN: 67886

European-Finnish (FIN) AF: 0.00220 AC: 100 AN: 45438

Middle Eastern (MID) AF: 0.00299 AC: 15 AN: 5014

European-Non Finnish (NFE) AF: 0.00216 AC: 2101 AN: 974504

Other (OTH) AF: 0.00431 AC: 220 AN: 51074

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000715 AC: 77 AN: 107726 Hom.: 1 Cov.: 17 AF XY: 0.000712 AC XY: 37 AN XY: 51976

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000516 AC: 14 AN: 27112

American (AMR) AF: 0.000943 AC: 9 AN: 9544

Ashkenazi Jewish (ASJ) AF: 0.000345 AC: 1 AN: 2902

East Asian (EAS) AF: 0.00253 AC: 6 AN: 2370

South Asian (SAS) AF: 0.00143 AC: 4 AN: 2798

European-Finnish (FIN) AF: 0.000128 AC: 1 AN: 7788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.000775 AC: 41 AN: 52914

Other (OTH) AF: 0.000681 AC: 1 AN: 1468

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0145 Hom.: 85

ExAC AF: 0.000386 AC: 41

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.23
DANN	Benign	0.43
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00075	N
LIST_S2	Benign	0.076	T
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-0.98	T
PhyloP100		-1.0
PrimateAI	Benign	0.35	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.016
Sift	Benign	1.0	T
Sift4G	Benign	0.52	T
Vest4		0.17
MutPred		0.40		Loss of ubiquitination at K40 (P = 0.0768)
MPC		0.010
ClinPred		0.00066	T
GERP RS		-5.1
gMVP		0.27
Mutation Taster		=97/3	polymorphism (auto)

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: rs200688856; hg19: chr1-161599779; COSMIC: COSV99670451;