Variant 1-161629801-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001244753.2(FCGR3B):c.296C>T(p.Pro99Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 1 hom., cov: 10)

Exomes 𝑓: 0.0000089 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

FCGR3B
NM_001244753.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR3B	NM_001244753.2 linkuse as main transcript	c.296C>T	p.Pro99Leu	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.296C>T	p.Pro99Leu	missense_variant	3/5		NM_001244753.2	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

76060

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000115

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000133

AC:

AN:

225430

Hom.:

AF XY:

0.0000244

AC XY:

AN XY:

122886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000893

AC:

AN:

1343346

Hom.:

Cov.:

AF XY:

0.0000120

AC XY:

AN XY:

667082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000692

Gnomad4 SAS exome

AF:

0.0000268

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000673

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000263

AC:

AN:

76060

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35632

show subpopulations

Gnomad4 AFR

AF:

0.000115

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000481

Hom.:

Bravo

AF:

0.0000113

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

Jul 09, 2021

The c.296C>T (p.P99L) alteration is located in exon 4 (coding exon 3) of the FCGR3B gene. This alteration results from a C to T substitution at nucleotide position 296, causing the proline (P) at amino acid position 99 to be replaced by a leucine (L). 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

Benign

0.24

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

.;.;T;.;.;.;T

Eigen

Benign

0.0086

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.91

.;.;D;D;D;D;D

M_CAP

Benign

0.0030

MetaRNN

Uncertain

0.53

D;D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-9.5

.;D;.;.;D;D;D

REVEL

Benign

0.12

Sift

Pathogenic

0.0

.;D;.;.;D;D;D

Sift4G

Uncertain

0.0020

.;D;D;D;D;D;.

Vest4

0.30, 0.31, 0.29, 0.34, 0.28

MutPred

0.69

Loss of disorder (P = 0.0764);Loss of disorder (P = 0.0764);.;.;Loss of disorder (P = 0.0764);.;.;

MVP

0.37

MPC

2.6

ClinPred

1.0

GERP RS

1.9

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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