NM_001244753.2:c.296C>T

Variant names:

• chr1-161629801-G-A
• rs267598137
• NM_001244753.2:c.296C>T

Variant summary

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

The NM_001244753.2(FCGR3B):​c.296C>T​(p.Pro99Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (1 hom., cov: 10)
  • Exomes 𝑓: 0.0000089 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• 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 0 ACMG points.

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.296C>T	p.Pro99Leu	missense	Exon 3 of 5	NP_001231682.2	A0A3B3ISU3
	FCGR3B	NM_000570.5		c.296C>T	p.Pro99Leu	missense	Exon 4 of 6	NP_000561.3	O75015
	FCGR3B	NM_001271035.2		c.293C>T	p.Pro98Leu	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.296C>T	p.Pro99Leu	missense	Exon 3 of 5	ENSP00000497461.1	A0A3B3ISU3
	ENSG00000289768	ENST00000699402.1		c.40+1254C>T		intron	N/A	ENSP00000514363.1	A0A8V8TN80
	FCGR3B	ENST00000367964.6	TSL:5	c.296C>T	p.Pro99Leu	missense	Exon 4 of 6	ENSP00000356941.2	O75015

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 2 AN: 76060 Hom.: 1 Cov.: 10

Gnomad AFR AF: 0.000115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000133 AC: 3 AN: 225430 AF XY: 0.0000244

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: 0.00

Gnomad NFE exome AF: 0.0000283

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000893 AC: 12 AN: 1343346 Hom.: 2 Cov.: 30 AF XY: 0.0000120 AC XY: 8 AN XY: 667082

African (AFR) AF: 0.00 AC: 0 AN: 27512

American (AMR) AF: 0.0000250 AC: 1 AN: 40028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24846

East Asian (EAS) AF: 0.0000692 AC: 2 AN: 28918

South Asian (SAS) AF: 0.0000268 AC: 2 AN: 74748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5244

European-Non Finnish (NFE) AF: 0.00000673 AC: 7 AN: 1040042

Other (OTH) AF: 0.00 AC: 0 AN: 54606

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000263 AC: 2 AN: 76060 Hom.: 1 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 35632

African (AFR) AF: 0.000115 AC: 2 AN: 17434

American (AMR) AF: 0.00 AC: 0 AN: 5758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2376

East Asian (EAS) AF: 0.00 AC: 0 AN: 1612

South Asian (SAS) AF: 0.00 AC: 0 AN: 1610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 210

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 40942

Other (OTH) AF: 0.00 AC: 0 AN: 968

Alfa AF: 0.0000481 Hom.: 0

Bravo AF: 0.0000113

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	Benign	0.24
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.0086
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.57	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0030	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.1	T
PhyloP100		3.1
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-9.5	D
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Vest4		0.30
MutPred		0.69		Loss of disorder (P = 0.0764)
MVP		0.37
MPC		2.6
ClinPred		1.0	D
GERP RS		1.9
gMVP		0.57
Mutation Taster		=84/16	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: rs267598137; hg19: chr1-161599591;