1-157544307-A-G

Variant summary

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

The NM_031281.3(FCRL5):ā€‹c.799T>Cā€‹(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: š‘“ 0.72 ( 40878 hom., cov: 33)
Exomes š‘“: 0.80 ( 475129 hom. )

Consequence

FCRL5
NM_031281.3 missense

Scores

18

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]

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
FCRL5NM_031281.3 linkuse as main transcriptc.799T>C p.Tyr267His missense_variant 5/17 ENST00000361835.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FCRL5ENST00000361835.8 linkuse as main transcriptc.799T>C p.Tyr267His missense_variant 5/171 NM_031281.3 P1Q96RD9-1
FCRL5ENST00000368190.7 linkuse as main transcriptc.799T>C p.Tyr267His missense_variant 5/101 Q96RD9-3
FCRL5ENST00000368189.3 linkuse as main transcriptc.799T>C p.Tyr267His missense_variant 5/81 Q96RD9-4
FCRL5ENST00000481082.1 linkuse as main transcriptn.997T>C non_coding_transcript_exon_variant 6/72

Frequencies

GnomAD3 genomes
AF:
0.716
AC:
108896
AN:
151986
Hom.:
40889
Cov.:
33
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.:
57
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.:
33
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
T
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
N
LIST_S2
Benign
0.30
T;T;T
MetaRNN
Benign
0.0000025
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-1.4
N;N;N
MutationTaster
Benign
1.0
P;P;P;P;P
PrimateAI
Benign
0.28
T
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
T
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.

Other links and lift over

dbSNP: rs6679793; hg19: chr1-157514097; COSMIC: COSV62511010; API