rs1050499

Variant names:

• chr1-161673197-A-T
• rs1050499
• NM_001394477.1:c.614A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (17 hom.)
• Consequence: FCGR2B NM_001394477.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.894
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000234211 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 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 ClinVar as [Benign]. Clinvar id is 3387964.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 17 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR2B	NM_001394477.1	c.614A>T	p.Tyr205Phe	missense_variant	Exon 4 of 8	ENST00000358671.10	NP_001381406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR2B	ENST00000358671.10	c.614A>T	p.Tyr205Phe	missense_variant	Exon 4 of 8	1	NM_001394477.1	ENSP00000351497.5

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

GnomAD2 exomes AF: 0.00236 AC: 582 AN: 246368 AF XY: 0.00239

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 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

African (AFR) AF: 0.00478 AC: 158 AN: 33058

American (AMR) AF: 0.00703 AC: 309 AN: 43954

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25946

East Asian (EAS) AF: 0.0104 AC: 410 AN: 39516

South Asian (SAS) AF: 0.00543 AC: 463 AN: 85234

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53234

Middle Eastern (MID) AF: 0.00440 AC: 25 AN: 5676

European-Non Finnish (NFE) AF: 0.000842 AC: 933 AN: 1108018

Other (OTH) AF: 0.00280 AC: 168 AN: 60072

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

African (AFR) AF: 0.00583 AC: 237 AN: 40636

American (AMR) AF: 0.0172 AC: 256 AN: 14854

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3458

East Asian (EAS) AF: 0.0137 AC: 70 AN: 5096

South Asian (SAS) AF: 0.00623 AC: 29 AN: 4654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00120 AC: 81 AN: 67680

Other (OTH) AF: 0.00241 AC: 5 AN: 2078

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FCGR2B: BP4, BS1, BS2 -

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
DEOGEN2	Benign	0.092	.;.;T
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
PhyloP100		0.89
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
Mutation Taster		=99/1	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: rs1050499; hg19: chr1-161642987; COSMIC: COSV52681360; COSMIC: COSV52681360;