Variant chr1-157544307-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031281.3(FCRL5):c.799T>C(p.Tyr267His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,613,752 control chromosomes in the GnomAD database, including 516,007 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 0.72 ( 40878 hom., cov: 33)

Exomes 𝑓: 0.80 ( 475129 hom. )

Consequence

FCRL5
NM_031281.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.06

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5442423E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL5	NM_031281.3 linkuse as main transcript	c.799T>C	p.Tyr267His	missense_variant	5/17	ENST00000361835.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL5	ENST00000361835.8 linkuse as main transcript	c.799T>C	p.Tyr267His	missense_variant	5/17	1	NM_031281.3	P1	Q96RD9-1
FCRL5	ENST00000368190.7 linkuse as main transcript	c.799T>C	p.Tyr267His	missense_variant	5/10	1			Q96RD9-3
FCRL5	ENST00000368189.3 linkuse as main transcript	c.799T>C	p.Tyr267His	missense_variant	5/8	1			Q96RD9-4
FCRL5	ENST00000481082.1 linkuse as main transcript	n.997T>C		non_coding_transcript_exon_variant	6/7	2

Frequencies

GnomAD3 genomes

AF:

0.716

AC:

108896

AN:

151986

Hom.:

40889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.846

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.809

Gnomad EAS

AF:

0.902

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.846

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.817

Gnomad OTH

AF:

0.745

GnomAD3 exomes

AF:

0.784

AC:

196913

AN:

251172

Hom.:

78510

AF XY:

0.791

AC XY:

107314

AN XY:

135732

show subpopulations

Gnomad AFR exome

AF:

0.460

Gnomad AMR exome

AF:

0.728

Gnomad ASJ exome

AF:

0.806

Gnomad EAS exome

AF:

0.901

Gnomad SAS exome

AF:

0.770

Gnomad FIN exome

AF:

0.849

Gnomad NFE exome

AF:

0.817

Gnomad OTH exome

AF:

0.799

GnomAD4 exome

AF:

0.804

AC:

1174775

AN:

1461648

Hom.:

475129

Cov.:

AF XY:

0.804

AC XY:

584607

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.453

Gnomad4 AMR exome

AF:

0.729

Gnomad4 ASJ exome

AF:

0.812

Gnomad4 EAS exome

AF:

0.915

Gnomad4 SAS exome

AF:

0.768

Gnomad4 FIN exome

AF:

0.846

Gnomad4 NFE exome

AF:

0.815

Gnomad4 OTH exome

AF:

0.789

GnomAD4 genome

AF:

0.716

AC:

108898

AN:

152104

Hom.:

40878

Cov.:

AF XY:

0.717

AC XY:

53306

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.469

Gnomad4 AMR

AF:

0.730

Gnomad4 ASJ

AF:

0.809

Gnomad4 EAS

AF:

0.902

Gnomad4 SAS

AF:

0.774

Gnomad4 FIN

AF:

0.846

Gnomad4 NFE

AF:

0.817

Gnomad4 OTH

AF:

0.746

Alfa

AF:

0.796

Hom.:

119023

Bravo

AF:

0.698

TwinsUK

AF:

0.821

AC:

3046

ALSPAC

AF:

0.819

AC:

3155

ESP6500AA

AF:

0.474

AC:

2089

ESP6500EA

AF:

0.813

AC:

6990

ExAC

AF:

0.781

AC:

94847

Asia WGS

AF:

0.809

AC:

2815

AN:

3478

EpiCase

AF:

0.808

EpiControl

AF:

0.805

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0050

DANN

Benign

0.20

DEOGEN2

Benign

0.00096

T;.;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.30

T;T;T

MetaRNN

Benign

0.0000025

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.4

N;N;N

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.012

Sift

Benign

0.60

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.048

MPC

0.086

ClinPred

0.00053

GERP RS

-6.0

Varity_R

0.014

gMVP

0.16

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