1-161626309-T-G

Variant names:

• chr1-161626309-T-G
• NM_001244753.2:c.413A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001244753.2(FCGR3B):​c.413A>C​(p.Lys138Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K138E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28291166).

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.413A>C	p.Lys138Thr	missense	Exon 4 of 5	NP_001231682.2	A0A3B3ISU3
	FCGR3B	NM_000570.5		c.413A>C	p.Lys138Thr	missense	Exon 5 of 6	NP_000561.3	O75015
	FCGR3B	NM_001271035.2		c.410A>C	p.Lys137Thr	missense	Exon 4 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.413A>C	p.Lys138Thr	missense	Exon 4 of 5	ENSP00000497461.1	A0A3B3ISU3
	ENSG00000289768	ENST00000699402.1		c.40+4746A>C		intron	N/A	ENSP00000514363.1	A0A8V8TN80
	FCGR3B	ENST00000367964.6	TSL:5	c.413A>C	p.Lys138Thr	missense	Exon 5 of 6	ENSP00000356941.2	O75015

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458724 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 725646

African (AFR) AF: 0.00 AC: 0 AN: 33140

American (AMR) AF: 0.00 AC: 0 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 85880

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110120

Other (OTH) AF: 0.0000166 AC: 1 AN: 60238

GnomAD4 genome Cov.: 29

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	0.61
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.5
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.088
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Vest4		0.57
MutPred		0.47		Loss of methylation at K138 (P = 0.0121)
MVP		0.29
MPC		0.60
ClinPred		0.96	D
GERP RS		2.4
gMVP		0.37
Mutation Taster		=65/35	polymorphism

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: chr1-161596099;