Genetic Variant FCRL3:p.Gly604Glu (chr1-157683244-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_052939.4(FCRL3):c.1811G>A(p.Gly604Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,424 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

FCRL3
NM_052939.4 missense, splice_region

Scores

Splicing: ADA: 0.004285

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.804

Publications

6 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029391348).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052939.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRL3	NM_052939.4	MANE Select	c.1811G>A	p.Gly604Glu	missense splice_region	Exon 11 of 15	NP_443171.2
FCRL3	NM_001320333.2		c.1811G>A	p.Gly604Glu	missense splice_region	Exon 11 of 16	NP_001307262.1	Q96P31-6
FCRL3	NR_135214.2		n.2033G>A		splice_region non_coding_transcript_exon	Exon 11 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRL3	ENST00000368184.8	TSL:1 MANE Select	c.1811G>A	p.Gly604Glu	missense splice_region	Exon 11 of 15	ENSP00000357167.3	Q96P31-1
FCRL3	ENST00000368186.9	TSL:1	c.1811G>A	p.Gly604Glu	missense splice_region	Exon 11 of 16	ENSP00000357169.5	Q96P31-6
FCRL3	ENST00000473231.5	TSL:1	n.2653G>A		splice_region non_coding_transcript_exon	Exon 5 of 9

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000578

AC:

145

AN:

250714

AF XY:

0.000531

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00125

AC:

1825

AN:

1461190

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

869

AN XY:

726898

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33422

American (AMR)

AF:

0.0000448

AC:

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.000192

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86176

European-Finnish (FIN)

AF:

0.0000936

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00159

AC:

1767

AN:

1111688

Other (OTH)

AF:

0.000679

AC:

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

177

266

354

443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.000749

AC:

114

AN:

152234

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41542

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

68008

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00117

Hom.:

Bravo

AF:

0.000722

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000535

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.00131

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.076

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.42

M_CAP

Benign

0.0032

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

0.80

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.038

Sift

Benign

0.092

Sift4G

Benign

0.062

Polyphen

0.096

Vest4

0.13

MVP

0.52

MPC

0.0060

ClinPred

0.028

GERP RS

2.4

Varity_R

0.14

gMVP

0.10

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0043

dbscSNV1_RF

Benign

0.13

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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