1-161671447-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001394477.1(FCGR2B):c.189G>A(p.Gln63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,603,124 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0064 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0062 (4 hom.)
• Consequence: FCGR2B NM_001394477.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.746

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=0.746 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR2B	NM_001394477.1	c.189G>A	p.Gln63=	synonymous_variant	3/8	ENST00000358671.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR2B	ENST00000358671.10	c.189G>A	p.Gln63=	synonymous_variant	3/8	1	NM_001394477.1	P4

Frequencies

GnomAD3 genomes AF: 0.00641 AC: 973 AN: 151796 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00841

Gnomad ASJ AF: 0.0145

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00768

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.00940

Gnomad OTH AF: 0.00962

GnomAD3 exomes AF: 0.00278 AC: 693 AN: 249478 Hom.: 0 AF XY: 0.00277 AC XY: 373 AN XY: 134726

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00478

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00221

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00374

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00615 AC: 8928 AN: 1451206 Hom.: 4 Cov.: 31 AF XY: 0.00618 AC XY: 4459 AN XY: 721994

Gnomad4 AFR exome AF: 0.00179

Gnomad4 AMR exome AF: 0.00366

Gnomad4 ASJ exome AF: 0.0105

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00533

Gnomad4 FIN exome AF: 0.000880

Gnomad4 NFE exome AF: 0.00672

Gnomad4 OTH exome AF: 0.00729

GnomAD4 genome AF: 0.00641 AC: 974 AN: 151918 Hom.: 0 Cov.: 29 AF XY: 0.00598 AC XY: 444 AN XY: 74280

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.00840

Gnomad4 ASJ AF: 0.0145

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00809

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00940

Gnomad4 OTH AF: 0.00904

Alfa AF: 0.00904 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	7.0
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs5017568; hg19: chr1-161641237; COSMIC: COSV52681235; COSMIC: COSV52681235;