rs1050499

chr1-161673197-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001394477.1(FCGR2B):c.614A>T(p.Tyr205Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,604,836 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (17 hom.)
• Consequence: FCGR2B NM_001394477.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054632127).
• BP6: Variant 1-161673197-A-T is Benign according to our data. Variant chr1-161673197-A-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00452 (679/150128) while in subpopulation AMR AF= 0.0172 (256/14854). AF 95% confidence interval is 0.0155. There are 0 homozygotes in gnomad4. There are 377 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR2B	NM_001394477.1	c.614A>T	p.Tyr205Phe	missense_variant	4/8	ENST00000358671.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR2B	ENST00000358671.10	c.614A>T	p.Tyr205Phe	missense_variant	4/8	1	NM_001394477.1	P4
	ENST00000453111.1	n.198-914T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00453 AC: 679 AN: 150016 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00585

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00120

Gnomad OTH AF: 0.00243

GnomAD3 exomes AF: 0.00236 AC: 582 AN: 246368 Hom.: 6 AF XY: 0.00239 AC XY: 319 AN XY: 133196

Gnomad AFR exome AF: 0.00352

Gnomad AMR exome AF: 0.00514

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00721

Gnomad SAS exome AF: 0.00410

Gnomad FIN exome AF: 0.0000468

Gnomad NFE exome AF: 0.000743

Gnomad OTH exome AF: 0.00250

GnomAD4 exome AF: 0.00171 AC: 2481 AN: 1454708 Hom.: 17 Cov.: 31 AF XY: 0.00185 AC XY: 1335 AN XY: 723322

Gnomad4 AFR exome AF: 0.00478

Gnomad4 AMR exome AF: 0.00703

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.0104

Gnomad4 SAS exome AF: 0.00543

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.000842

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome AF: 0.00452 AC: 679 AN: 150128 Hom.: 0 Cov.: 32 AF XY: 0.00514 AC XY: 377 AN XY: 73300

Gnomad4 AFR AF: 0.00583

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.0137

Gnomad4 SAS AF: 0.00623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00120

Gnomad4 OTH AF: 0.00241

Alfa AF: 0.00187 Hom.: 0

ESP6500AA AF: 0.00137 AC: 6

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00185 AC: 224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	4.6
Dann	Benign	0.56
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.12	T;T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.0055	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;.;L
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.075
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0010	B;B;B
Vest4		0.15
MVP		0.072
MPC		0.69
ClinPred		0.0069	T
GERP RS		1.2
Varity_R		0.44
gMVP		0.17

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: rs1050499; hg19: chr1-161642987; COSMIC: COSV52681360; COSMIC: COSV52681360;