Genetic Variant ENST00000480308.5:n.2418A>C (chr1-161675681-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B.

-12

BP4_StrongBA1

The ENST00000480308.5(FCGR2B):n.2418A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 243,030 control chromosomes in the GnomAD database, including 83,268 homozygotes. 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 0.83 ( 52264 hom., cov: 29)

Exomes 𝑓: 0.82 ( 31004 hom. )

Consequence

FCGR2B
ENST00000480308.5 non_coding_transcript_exon

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: Labcorp Genetics (formerly Invitae), Orphanet

FCGR2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR2B	NM_001394477.1 link	c.817+368A>C		intron_variant	Intron 6 of 7	ENST00000358671.10	NP_001381406.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCGR2B	ENST00000480308.5 link	n.2418A>C	non_coding_transcript_exon_variant	Exon 5 of 6	1
FCGR2B	ENST00000358671.10 link	c.817+368A>C	intron_variant	Intron 6 of 7	1	NM_001394477.1	ENSP00000351497.5	P31994-1
FCGR2B	ENST00000367961.8 link	c.796+368A>C	intron_variant	Intron 5 of 6	1		ENSP00000356938.4	P31994-3
FCGR2B	ENST00000236937.13 link	c.760+1608A>C	intron_variant	Intron 5 of 6	1		ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes

AF:

0.827

AC:

125592

AN:

151816

Hom.:

52221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.757

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.859

Gnomad ASJ

AF:

0.790

Gnomad EAS

AF:

0.787

Gnomad SAS

AF:

0.808

Gnomad FIN

AF:

0.892

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.861

Gnomad OTH

AF:

0.842

GnomAD4 exome

AF:

0.823

AC:

74941

AN:

91096

Hom.:

31004

Cov.:

AF XY:

0.823

AC XY:

34979

AN XY:

42482

show subpopulations

African (AFR)

AF:

0.760

AC:

3178

AN:

4182

American (AMR)

AF:

0.855

AC:

2299

AN:

2688

Ashkenazi Jewish (ASJ)

AF:

0.784

AC:

4248

AN:

5420

East Asian (EAS)

AF:

0.697

AC:

8120

AN:

11656

South Asian (SAS)

AF:

0.775

AC:

869

AN:

1122

European-Finnish (FIN)

AF:

0.848

AC:

833

AN:

982

Middle Eastern (MID)

AF:

0.845

AC:

465

AN:

550

European-Non Finnish (NFE)

AF:

0.854

AC:

48772

AN:

57080

Other (OTH)

AF:

0.830

AC:

6157

AN:

7416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

705

1410

2115

2820

3525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.827

AC:

125693

AN:

151934

Hom.:

52264

Cov.:

AF XY:

0.829

AC XY:

61563

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.757

AC:

31341

AN:

41394

American (AMR)

AF:

0.860

AC:

13124

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

2739

AN:

3466

East Asian (EAS)

AF:

0.787

AC:

4067

AN:

5168

South Asian (SAS)

AF:

0.808

AC:

3884

AN:

4806

European-Finnish (FIN)

AF:

0.892

AC:

9429

AN:

10568

Middle Eastern (MID)

AF:

0.806

AC:

237

AN:

294

European-Non Finnish (NFE)

AF:

0.861

AC:

58495

AN:

67954

Other (OTH)

AF:

0.843

AC:

1775

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1042

2085

3127

4170

5212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<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:

0.813

Hom.:

2414

Bravo

AF:

0.822

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.25

(source)

DANN

Benign

0.47

PhyloP100

-0.56

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over