Genetic Variant FCGR2B:c.817+368A>T (chr1-161675681-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394477.1(FCGR2B):c.817+368A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 151,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000055 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FCGR2B
NM_001394477.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.559

Publications

2 publications found

Variant links:

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)

FCGR2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCGR2B	NM_001394477.1	MANE Select	c.817+368A>T	intron	N/A	NP_001381406.1	P31994-1
FCGR2B	NM_004001.5		c.817+368A>T	intron	N/A	NP_003992.3
FCGR2B	NM_001002275.3		c.814+368A>T	intron	N/A	NP_001002275.1	P31994-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCGR2B	ENST00000358671.10	TSL:1 MANE Select	c.817+368A>T	intron	N/A	ENSP00000351497.5	P31994-1
FCGR2B	ENST00000367961.8	TSL:1	c.796+368A>T	intron	N/A	ENSP00000356938.4	P31994-3
FCGR2B	ENST00000236937.13	TSL:1	c.760+1608A>T	intron	N/A	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000548

AC:

AN:

91184

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

42522

show subpopulations

African (AFR)

AF:

0.000717

AC:

AN:

4182

American (AMR)

AF:

0.00

AC:

AN:

2688

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5424

East Asian (EAS)

AF:

0.00

AC:

AN:

11676

South Asian (SAS)

AF:

0.00

AC:

AN:

1124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

550

European-Non Finnish (NFE)

AF:

0.0000350

AC:

AN:

57134

Other (OTH)

AF:

0.00

AC:

AN:

7418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000112

AC:

AN:

151874

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.000339

AC:

AN:

41302

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

2414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.25

(source)

DANN

Benign

0.49

PhyloP100

-0.56

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over