1-157586291-G-A

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

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.751
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]

Genome browser will be placed here

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
FCRL4NM_031282.3 linkuse as main transcriptc.1012C>T p.Arg338Cys missense_variant 6/12 ENST00000271532.2 NP_112572.1 Q96PJ5-1
FCRL4XM_011510034.2 linkuse as main transcriptc.1009C>T p.Arg337Cys missense_variant 6/12 XP_011508336.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FCRL4ENST00000271532.2 linkuse as main transcriptc.1012C>T p.Arg338Cys missense_variant 6/121 NM_031282.3 ENSP00000271532.1 Q96PJ5-1
FCRL4ENST00000448509.6 linkuse as main transcriptn.753C>T non_coding_transcript_exon_variant 4/92

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152058
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250742
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135520
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461824
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152058
Hom.:
0
Cov.:
31
AF XY:
0.0000943
AC XY:
7
AN XY:
74250
show subpopulations
Gnomad4 AFR
AF:
0.000338
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.000110
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsFeb 16, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.036
T
Eigen
Benign
-0.027
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.80
T
M_CAP
Benign
0.0061
T
MetaRNN
Uncertain
0.56
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.1
M
PrimateAI
Benign
0.28
T
PROVEAN
Pathogenic
-5.5
D
REVEL
Benign
0.13
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0020
D
Polyphen
0.99
D
Vest4
0.56
MVP
0.46
MPC
0.25
ClinPred
0.59
D
GERP RS
2.2
Varity_R
0.25
gMVP
0.31

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: rs761378641; hg19: chr1-157556081; API