chr1-161675262-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001394477.1(FCGR2B):c.766C>T(p.Pro256Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 1,599,402 control chromosomes in the GnomAD database, including 229 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 140 hom., cov: 31)

Exomes 𝑓: 0.0046 ( 89 hom. )

Consequence

FCGR2B
NM_001394477.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.600

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003109455).

BP6

Variant 1-161675262-C-T is Benign according to our data. Variant chr1-161675262-C-T is described in ClinVar as Benign. ClinVar VariationId is 779299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
FCGR2B	NM_001394477.1	MANE Select	c.766C>T	p.Pro256Ser	missense	Exon 6 of 8	NP_001381406.1	P31994-1
FCGR2B	NM_004001.5		c.766C>T	p.Pro256Ser	missense	Exon 7 of 9	NP_003992.3
FCGR2B	NM_001002275.3		c.763C>T	p.Pro255Ser	missense	Exon 7 of 9	NP_001002275.1	P31994-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCGR2B	ENST00000358671.10	TSL:1 MANE Select	c.766C>T	p.Pro256Ser	missense	Exon 6 of 8	ENSP00000351497.5	P31994-1
FCGR2B	ENST00000367961.8	TSL:1	c.745C>T	p.Pro249Ser	missense	Exon 5 of 7	ENSP00000356938.4	P31994-3
FCGR2B	ENST00000236937.13	TSL:1	c.760+1189C>T		intron	N/A	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4113

AN:

151984

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0821

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.00543

Gnomad OTH

AF:

0.0192

GnomAD2 exomes

AF:

0.00559

AC:

1353

AN:

241958

AF XY:

0.00475

show subpopulations

Gnomad AFR exome

AF:

0.0436

Gnomad AMR exome

AF:

0.00607

Gnomad ASJ exome

AF:

0.00142

Gnomad EAS exome

AF:

0.000509

Gnomad FIN exome

AF:

0.00270

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00829

GnomAD4 exome

AF:

0.00457

AC:

6611

AN:

1447300

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

3085

AN XY:

719868

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0566

AC:

1776

AN:

31380

American (AMR)

AF:

0.00700

AC:

307

AN:

43832

Ashkenazi Jewish (ASJ)

AF:

0.00220

AC:

AN:

25932

East Asian (EAS)

AF:

0.000358

AC:

AN:

39128

South Asian (SAS)

AF:

0.00383

AC:

324

AN:

84620

European-Finnish (FIN)

AF:

0.00394

AC:

210

AN:

53268

Middle Eastern (MID)

AF:

0.00693

AC:

AN:

4616

European-Non Finnish (NFE)

AF:

0.00312

AC:

3442

AN:

1104822

Other (OTH)

AF:

0.00752

AC:

449

AN:

59702

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.351

Heterozygous variant carriers

298

595

893

1190

1488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

276

414

552

690

<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:

0.0271

AC:

4125

AN:

152102

Hom.:

140

Cov.:

AF XY:

0.0266

AC XY:

1977

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0822

AC:

3403

AN:

41396

American (AMR)

AF:

0.0143

AC:

218

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00601

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00292

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00543

AC:

369

AN:

68004

Other (OTH)

AF:

0.0190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

177

354

531

708

885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0135

Hom.:

Bravo

AF:

0.0301

ExAC

AF:

0.00619

AC:

752

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.19

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.062

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0031

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.0

PhyloP100

-0.60

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.1

REVEL

Benign

0.016

Sift

Benign

0.20

Sift4G

Benign

0.62

Polyphen

0.30

Vest4

0.083

MVP

0.12

MPC

0.76

ClinPred

0.010

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.18

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over