Variant 1-161629848-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001244753.2(FCGR3B):c.249C>G(p.Asp83Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,426,558 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 6 hom., cov: 10)

Exomes 𝑓: 0.000030 ( 4 hom. )

Consequence

FCGR3B
NM_001244753.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

FCGR3B (HGNC:3620): (Fc gamma receptor IIIb) The protein encoded by this gene is a low affinity receptor for the Fc region of gamma immunoglobulins (IgG). The encoded protein acts as a monomer and can bind either monomeric or aggregated IgG. This gene may function to capture immune complexes in the peripheral circulation. Several transcript variants encoding different isoforms have been found for this gene. A highly-similar gene encoding a related protein is also found on chromosome 1. [provided by RefSeq, Aug 2012]

FCGR3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022362798).

BS2

High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR3B	NM_001244753.2 linkuse as main transcript	c.249C>G	p.Asp83Glu	missense_variant	3/5	ENST00000650385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR3B	ENST00000650385.1 linkuse as main transcript	c.249C>G	p.Asp83Glu	missense_variant	3/5		NM_001244753.2	P2

Frequencies

GnomAD3 genomes

AF:

0.000459

AC:

AN:

78446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000335

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:

0.0000470

Gnomad OTH

AF:

0.00198

GnomAD3 exomes

AF:

0.000101

AC:

AN:

227300

Hom.:

AF XY:

0.0000567

AC XY:

AN XY:

123560

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.000164

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000942

Gnomad OTH exome

AF:

0.000350

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1348056

Hom.:

Cov.:

AF XY:

0.0000328

AC XY:

AN XY:

671404

show subpopulations

Gnomad4 AFR exome

AF:

0.000976

Gnomad4 AMR exome

AF:

0.000171

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.63e-7

Gnomad4 OTH exome

AF:

0.0000729

GnomAD4 genome

AF:

0.000459

AC:

AN:

78502

Hom.:

Cov.:

AF XY:

0.000434

AC XY:

AN XY:

36894

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.000335

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000470

Gnomad4 OTH

AF:

0.00195

Alfa

AF:

0.000337

Hom.:

ESP6500AA

AF:

0.000237

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000921

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2023

The c.249C>G (p.D83E) alteration is located in exon 4 (coding exon 3) of the FCGR3B gene. This alteration results from a C to G substitution at nucleotide position 249, causing the aspartic acid (D) at amino acid position 83 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.44

MetaRNN

Benign

0.022

T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.37

Vest4

0.40, 0.40, 0.41, 0.41, 0.44

MutPred

0.58

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);.;.;Gain of loop (P = 0.1069);.;.;

MVP

0.35

MPC

2.0

ClinPred

0.068

GERP RS

1.9

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over