Genetic Variant FCRL5:p.Val466Ile (chr1-157539092-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_031281.3(FCRL5):c.1396G>A(p.Val466Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,612,654 control chromosomes in the GnomAD database, including 557,643 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.72 ( 42905 hom., cov: 34)

Exomes 𝑓: 0.84 ( 514738 hom. )

Consequence

FCRL5
NM_031281.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.49

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:

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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=1.2775563E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL5	NM_031281.3 link	c.1396G>A	p.Val466Ile	missense_variant	Exon 7 of 17	ENST00000361835.8	NP_112571.2	Q96RD9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FCRL5	ENST00000361835.8 link	c.1396G>A	p.Val466Ile	missense_variant	Exon 7 of 17	1	NM_031281.3	ENSP00000354691.3	Q96RD9-1
FCRL5	ENST00000368190.7 link	c.1396G>A	p.Val466Ile	missense_variant	Exon 7 of 10	1		ENSP00000357173.3	Q96RD9-3
FCRL5	ENST00000368189.3 link	c.1396G>A	p.Val466Ile	missense_variant	Exon 7 of 8	1		ENSP00000357172.3	Q96RD9-4

Frequencies

GnomAD3 genomes

AF:

0.724

AC:

110067

AN:

152126

Hom.:

42910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.820

Gnomad AMR

AF:

0.798

Gnomad ASJ

AF:

0.875

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.859

Gnomad FIN

AF:

0.884

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.853

Gnomad OTH

AF:

0.767

GnomAD3 exomes

AF:

0.820

AC:

204897

AN:

249900

Hom.:

85832

AF XY:

0.831

AC XY:

112215

AN XY:

135050

show subpopulations

Gnomad AFR exome

AF:

0.389

Gnomad AMR exome

AF:

0.828

Gnomad ASJ exome

AF:

0.875

Gnomad EAS exome

AF:

0.780

Gnomad SAS exome

AF:

0.859

Gnomad FIN exome

AF:

0.884

Gnomad NFE exome

AF:

0.857

Gnomad OTH exome

AF:

0.848

GnomAD4 exome

AF:

0.836

AC:

1221158

AN:

1460410

Hom.:

514738

Cov.:

AF XY:

0.839

AC XY:

609523

AN XY:

726450

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.825

Gnomad4 ASJ exome

AF:

0.872

Gnomad4 EAS exome

AF:

0.761

Gnomad4 SAS exome

AF:

0.859

Gnomad4 FIN exome

AF:

0.882

Gnomad4 NFE exome

AF:

0.849

Gnomad4 OTH exome

AF:

0.818

GnomAD4 genome

AF:

0.723

AC:

110081

AN:

152244

Hom.:

42905

Cov.:

AF XY:

0.727

AC XY:

54131

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.401

Gnomad4 AMR

AF:

0.798

Gnomad4 ASJ

AF:

0.875

Gnomad4 EAS

AF:

0.776

Gnomad4 SAS

AF:

0.859

Gnomad4 FIN

AF:

0.884

Gnomad4 NFE

AF:

0.853

Gnomad4 OTH

AF:

0.766

Alfa

AF:

0.829

Hom.:

129949

Bravo

AF:

0.702

TwinsUK

AF:

0.854

AC:

3168

ALSPAC

AF:

0.853

AC:

3286

ESP6500AA

AF:

0.408

AC:

1796

ESP6500EA

AF:

0.849

AC:

7298

ExAC

AF:

0.813

AC:

98734

Asia WGS

AF:

0.784

AC:

2727

AN:

3478

EpiCase

AF:

0.855

EpiControl

AF:

0.852

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.011

DANN

Benign

0.97

DEOGEN2

Benign

0.0026

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0089

LIST_S2

Benign

0.50

T;T;T

MetaRNN

Benign

0.0000013

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

L;L;L

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.28

N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.13

B;B;P

Vest4

0.048

MPC

0.060

ClinPred

0.0063

GERP RS

-1.7

Varity_R

0.067

gMVP

0.094

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over