rs543549325

Variant names:

• chr1-161671401-C-A
• rs543549325
• NM_001394477.1:c.143C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-161671401-C-A
• chr1-161671401-C-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001394477.1(FCGR2B):​c.143C>A​(p.Pro48Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: FCGR2B NM_001394477.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• Publications: 1 publications found

Genes affected

FCGR2B (HGNC:3618): (Fc gamma receptor IIb) The protein encoded by this gene is a low affinity receptor for the Fc region of immunoglobulin gamma complexes. The encoded protein is involved in the phagocytosis of immune complexes and in the regulation of antibody production by B-cells. Variations in this gene may increase susceptibilty to systemic lupus erythematosus (SLE). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

FCGR2B Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE, NO_KNOWN Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3637973).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394477.1. 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
	FCGR2B	NM_001394477.1	MANE Select	c.143C>A	p.Pro48Gln	missense	Exon 3 of 8	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.143C>A	p.Pro48Gln	missense	Exon 4 of 9	NP_003992.3
	FCGR2B	NM_001002275.3		c.140C>A	p.Pro47Gln	missense	Exon 4 of 9	NP_001002275.1	P31994-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2B	ENST00000358671.10	TSL:1 MANE Select	c.143C>A	p.Pro48Gln	missense	Exon 3 of 8	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.122C>A	p.Pro41Gln	missense	Exon 2 of 7	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.143C>A	p.Pro48Gln	missense	Exon 3 of 7	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000478 AC: 12 AN: 251136 AF XY: 0.0000736

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000280 AC: 41 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000301 AC: 26 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		2.4
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.19
Sift	Benign	0.077	T
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.28
MutPred		0.43		Loss of glycosylation at P48 (P = 0.0098)
MVP		0.62
MPC		1.7
ClinPred		0.79	D
GERP RS		4.5
Varity_R		0.46
gMVP		0.37
Mutation Taster		=85/15	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

dbSNP: rs543549325; hg19: chr1-161641191;