1-161671477-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.219G>A(p.Gly73=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,613,888 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0070 (2 hom.)
• Consequence: FCGR2B NM_001394477.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.545

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=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.545 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR2B	NM_001394477.1	c.219G>A	p.Gly73=	synonymous_variant	3/8	ENST00000358671.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR2B	ENST00000358671.10	c.219G>A	p.Gly73=	synonymous_variant	3/8	1	NM_001394477.1	P4

Frequencies

GnomAD3 genomes AF: 0.00540 AC: 822 AN: 152130 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00897

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00798

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00528 AC: 1327 AN: 251438 Hom.: 1 AF XY: 0.00540 AC XY: 734 AN XY: 135888

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00448

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.00431

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00731

Gnomad OTH exome AF: 0.00733

GnomAD4 exome AF: 0.00702 AC: 10258 AN: 1461640 Hom.: 2 Cov.: 31 AF XY: 0.00695 AC XY: 5052 AN XY: 727124

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00445

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00452

Gnomad4 FIN exome AF: 0.000543

Gnomad4 NFE exome AF: 0.00783

Gnomad4 OTH exome AF: 0.00813

GnomAD4 genome AF: 0.00539 AC: 821 AN: 152248 Hom.: 0 Cov.: 29 AF XY: 0.00517 AC XY: 385 AN XY: 74440

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00896

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00798

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00783 Hom.: 1

EpiCase AF: 0.00992

EpiControl AF: 0.00890

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	-0.84
Cadd	Benign	1.0
Dann	Benign	0.78

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: rs144573139; hg19: chr1-161641267; COSMIC: COSV52683461; COSMIC: COSV52683461;