rs765263802

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_031282.3(FCRL4):​c.1096G>T​(p.Gly366Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G366S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FCRL4
NM_031282.3 missense

Scores

3
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.187
Variant links:
Genes affected
FCRL4 (HGNC:18507): (Fc receptor like 4) 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 has four extracellular C2-type immunoglobulin domains, a transmembrane domain and a cytoplasmic domain that contains three immune-receptor tyrosine-based inhibitory motifs. This protein may play a role in the function of memory B-cells in the epithelia. Aberrations in the chromosomal region encoding this gene are associated with non-Hodgkin lymphoma and multiple myeloma. [provided by RefSeq, Apr 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FCRL4NM_031282.3 linkc.1096G>T p.Gly366Cys missense_variant Exon 6 of 12 ENST00000271532.2 NP_112572.1 Q96PJ5-1
FCRL4XM_011510034.2 linkc.1093G>T p.Gly365Cys missense_variant Exon 6 of 12 XP_011508336.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FCRL4ENST00000271532.2 linkc.1096G>T p.Gly366Cys missense_variant Exon 6 of 12 1 NM_031282.3 ENSP00000271532.1 Q96PJ5-1
FCRL4ENST00000448509.6 linkn.837G>T non_coding_transcript_exon_variant Exon 4 of 9 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461604
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.0022
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.035
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Uncertain
0.15
D
MutationAssessor
Pathogenic
4.4
H
PrimateAI
Benign
0.31
T
PROVEAN
Pathogenic
-6.5
D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.51
MutPred
0.75
Loss of phosphorylation at Y365 (P = 0.1176);
MVP
0.93
MPC
0.26
ClinPred
0.88
D
GERP RS
1.1
Varity_R
0.40
gMVP
0.57

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.

Other links and lift over

dbSNP: rs765263802; hg19: chr1-157555997; API