Variant 1-157698600-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_052939.4(FCRL3):c.82A>G(p.Asn28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,612,742 control chromosomes in the GnomAD database, including 180,413 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.50 ( 19728 hom., cov: 32)

Exomes 𝑓: 0.47 ( 160685 hom. )

Consequence

FCRL3
NM_052939.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.572

Variant links:

Genes affected

FCRL3 (HGNC:18506): (Fc receptor like 3) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein contains immunoreceptor-tyrosine activation motifs and immunoreceptor-tyrosine inhibitory motifs in its cytoplasmic domain and may play a role in regulation of the immune system. Mutations in this gene have been associated with rheumatoid arthritis, autoimmune thyroid disease, and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

FCRL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.182872E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL3	NM_052939.4 linkuse as main transcript	c.82A>G	p.Asn28Asp	missense_variant	4/15	ENST00000368184.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL3	ENST00000368184.8 linkuse as main transcript	c.82A>G	p.Asn28Asp	missense_variant	4/15	1	NM_052939.4	P2	Q96P31-1

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76408

AN:

151948

Hom.:

19697

Cov.:

show subpopulations

Gnomad AFR

AF:

0.628

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.497

GnomAD3 exomes

AF:

0.448

AC:

112568

AN:

251050

Hom.:

25906

AF XY:

0.438

AC XY:

59412

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.633

Gnomad AMR exome

AF:

0.457

Gnomad ASJ exome

AF:

0.473

Gnomad EAS exome

AF:

0.404

Gnomad SAS exome

AF:

0.315

Gnomad FIN exome

AF:

0.421

Gnomad NFE exome

AF:

0.465

Gnomad OTH exome

AF:

0.456

GnomAD4 exome

AF:

0.466

AC:

680949

AN:

1460678

Hom.:

160685

Cov.:

AF XY:

0.460

AC XY:

334394

AN XY:

726734

show subpopulations

Gnomad4 AFR exome

AF:

0.633

Gnomad4 AMR exome

AF:

0.453

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.404

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.429

Gnomad4 NFE exome

AF:

0.477

Gnomad4 OTH exome

AF:

0.475

GnomAD4 genome

AF:

0.503

AC:

76482

AN:

152064

Hom.:

19728

Cov.:

AF XY:

0.497

AC XY:

36945

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.628

Gnomad4 AMR

AF:

0.473

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.309

Gnomad4 FIN

AF:

0.432

Gnomad4 NFE

AF:

0.465

Gnomad4 OTH

AF:

0.499

Alfa

AF:

0.471

Hom.:

43944

Bravo

AF:

0.517

TwinsUK

AF:

0.492

AC:

1824

ALSPAC

AF:

0.475

AC:

1829

ESP6500AA

AF:

0.628

AC:

2767

ESP6500EA

AF:

0.465

AC:

3995

ExAC

AF:

0.450

AC:

54625

Asia WGS

AF:

0.421

AC:

1464

AN:

3478

EpiCase

AF:

0.463

EpiControl

AF:

0.469

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.0080

DANN

Benign

0.50

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.073

T;T;T

MetaRNN

Benign

0.0000062

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.46

N;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.95

N;N;.

REVEL

Benign

0.047

Sift

Benign

1.0

T;T;.

Sift4G

Benign

0.72

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.021

MPC

0.0061

ClinPred

0.025

GERP RS

-11

Varity_R

0.043

gMVP

0.056

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over