1-157586291-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_031282.3(FCRL4):c.1012C>T(p.Arg338Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
FCRL4
NM_031282.3 missense
NM_031282.3 missense
Scores
2
4
13
Clinical Significance
Conservation
PhyloP100: 0.751
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FCRL4 | NM_031282.3 | c.1012C>T | p.Arg338Cys | missense_variant | 6/12 | ENST00000271532.2 | NP_112572.1 | |
FCRL4 | XM_011510034.2 | c.1009C>T | p.Arg337Cys | missense_variant | 6/12 | XP_011508336.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FCRL4 | ENST00000271532.2 | c.1012C>T | p.Arg338Cys | missense_variant | 6/12 | 1 | NM_031282.3 | ENSP00000271532.1 | ||
FCRL4 | ENST00000448509.6 | n.753C>T | non_coding_transcript_exon_variant | 4/9 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152058Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250742Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135520
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727212
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GnomAD4 genome AF: 0.0000986 AC: 15AN: 152058Hom.: 0 Cov.: 31 AF XY: 0.0000943 AC XY: 7AN XY: 74250
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 16, 2023 | The c.1012C>T (p.R338C) alteration is located in exon 6 (coding exon 6) of the FCRL4 gene. This alteration results from a C to T substitution at nucleotide position 1012, causing the arginine (R) at amino acid position 338 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at