rs12118043

Variant names:

• chr1-161677034-C-A
• rs12118043
• NM_001394477.1:c.818-294C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394477.1(FCGR2B):​c.818-294C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 461,422 control chromosomes in the GnomAD database, including 6,104 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1770 hom., cov: 31)
  • Exomes 𝑓: 0.15 (4334 hom.)
• Consequence: FCGR2B NM_001394477.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

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.818-294C>A		intron	N/A	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.818-294C>A		intron	N/A	NP_003992.3
	FCGR2B	NM_001002275.3		c.815-294C>A		intron	N/A	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.818-294C>A		intron	N/A	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.797-294C>A		intron	N/A	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.761-294C>A		intron	N/A	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20087 AN: 152014 Hom.: 1770 Cov.: 31

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.0563

Gnomad SAS AF: 0.0996

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.153 AC: 47459 AN: 309290 Hom.: 4334 Cov.: 0 AF XY: 0.149 AC XY: 24165 AN XY: 162064

African (AFR) AF: 0.0358 AC: 261 AN: 7288

American (AMR) AF: 0.0892 AC: 659 AN: 7386

Ashkenazi Jewish (ASJ) AF: 0.0917 AC: 956 AN: 10420

East Asian (EAS) AF: 0.0441 AC: 806 AN: 18272

South Asian (SAS) AF: 0.103 AC: 3176 AN: 30864

European-Finnish (FIN) AF: 0.177 AC: 3813 AN: 21564

Middle Eastern (MID) AF: 0.0867 AC: 133 AN: 1534

European-Non Finnish (NFE) AF: 0.180 AC: 34778 AN: 193050

Other (OTH) AF: 0.152 AC: 2877 AN: 18912

GnomAD4 genome AF: 0.132 AC: 20079 AN: 152132 Hom.: 1770 Cov.: 31 AF XY: 0.128 AC XY: 9505 AN XY: 74372

African (AFR) AF: 0.0357 AC: 1483 AN: 41532

American (AMR) AF: 0.104 AC: 1588 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3470

East Asian (EAS) AF: 0.0561 AC: 290 AN: 5172

South Asian (SAS) AF: 0.100 AC: 483 AN: 4814

European-Finnish (FIN) AF: 0.188 AC: 1991 AN: 10582

Middle Eastern (MID) AF: 0.0925 AC: 27 AN: 292

European-Non Finnish (NFE) AF: 0.197 AC: 13410 AN: 67960

Other (OTH) AF: 0.143 AC: 302 AN: 2112

Alfa AF: 0.170 Hom.: 4119

Bravo AF: 0.124

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.2
DANN	Benign	0.88
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12118043; hg19: chr1-161646824;