Genetic Variant FCRL5:p.Val269Ile (chr1-157544301-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_031281.3(FCRL5):c.805G>A(p.Val269Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,613,592 control chromosomes in the GnomAD database, including 36,126 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4061 hom., cov: 32)

Exomes 𝑓: 0.21 ( 32065 hom. )

Consequence

FCRL5
NM_031281.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.22

Publications

30 publications found

Variant links:

Genes affected

FCRL5 (HGNC:18508): (Fc receptor like 5) This gene encodes a member of the immunoglobulin receptor superfamily and the Fc-receptor like family. This gene and several other Fc receptor-like gene members are clustered on the long arm of chromosome 1. The encoded protein is a single-pass type I membrane protein and contains 8 immunoglobulin-like C2-type domains. This gene is implicated in B cell development and lymphomagenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Sep 2010]

FCRL5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034855008).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL5	NM_031281.3 link	c.805G>A	p.Val269Ile	missense_variant	Exon 5 of 17	ENST00000361835.8	NP_112571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
FCRL5	ENST00000361835.8 link	c.805G>A	p.Val269Ile	missense_variant	Exon 5 of 17	1	NM_031281.3	ENSP00000354691.3
FCRL5	ENST00000368190.7 link	c.805G>A	p.Val269Ile	missense_variant	Exon 5 of 10	1		ENSP00000357173.3
FCRL5	ENST00000368189.3 link	c.805G>A	p.Val269Ile	missense_variant	Exon 5 of 8	1		ENSP00000357172.3
FCRL5	ENST00000481082.1 link	n.1003G>A		non_coding_transcript_exon_variant	Exon 6 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34349

AN:

152032

Hom.:

4064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.0830

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.252

GnomAD2 exomes

AF:

0.189

AC:

47581

AN:

251146

AF XY:

0.191

show subpopulations

Gnomad AFR exome

AF:

0.297

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.0849

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.206

AC:

300463

AN:

1461442

Hom.:

32065

Cov.:

AF XY:

0.205

AC XY:

148855

AN XY:

727034

show subpopulations

African (AFR)

AF:

0.297

AC:

9935

AN:

33466

American (AMR)

AF:

0.134

AC:

5975

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

5887

AN:

26132

East Asian (EAS)

AF:

0.0781

AC:

3102

AN:

39700

South Asian (SAS)

AF:

0.177

AC:

15249

AN:

86246

European-Finnish (FIN)

AF:

0.197

AC:

10532

AN:

53420

Middle Eastern (MID)

AF:

0.288

AC:

1659

AN:

5766

European-Non Finnish (NFE)

AF:

0.212

AC:

235277

AN:

1111608

Other (OTH)

AF:

0.213

AC:

12847

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

12715

25429

38144

50858

63573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8094

16188

24282

32376

40470

<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:

0.226

AC:

34359

AN:

152150

Hom.:

4061

Cov.:

AF XY:

0.221

AC XY:

16414

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.294

AC:

12192

AN:

41488

American (AMR)

AF:

0.184

AC:

2805

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

815

AN:

3470

East Asian (EAS)

AF:

0.0828

AC:

428

AN:

5170

South Asian (SAS)

AF:

0.160

AC:

773

AN:

4828

European-Finnish (FIN)

AF:

0.209

AC:

2209

AN:

10580

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14267

AN:

68018

Other (OTH)

AF:

0.253

AC:

535

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1385

2770

4155

5540

6925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.206

Hom.:

3061

Bravo

AF:

0.227

TwinsUK

AF:

0.226

AC:

837

ESP6500AA

AF:

0.294

AC:

1295

ESP6500EA

AF:

0.214

AC:

1842

ExAC

AF:

0.192

AC:

23339

Asia WGS

AF:

0.156

AC:

545

AN:

3478

EpiCase

AF:

0.218

EpiControl

AF:

0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.028

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0026

T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

LIST_S2

Benign

0.26

T;T;T

MetaRNN

Benign

0.0035

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.68

N;N;N

PhyloP100

-2.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.37

N;N;N

Sift

Benign

0.69

T;T;T

Sift4G

Benign

0.47

T;T;T

Vest4

0.023

ClinPred

0.0015

GERP RS

-1.6

Varity_R

0.011

gMVP

0.089

Mutation Taster

=100/0

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over