1-157586294-G-C

Position:

• chr1-157586294-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031282.3(FCRL4):​c.1009C>G​(p.Gln337Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FCRL4 NM_031282.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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]

FCRL4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1484642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL4	NM_031282.3	c.1009C>G	p.Gln337Glu	missense_variant	6/12	ENST00000271532.2	NP_112572.1
FCRL4	XM_011510034.2	c.1006C>G	p.Gln336Glu	missense_variant	6/12		XP_011508336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL4	ENST00000271532.2	c.1009C>G	p.Gln337Glu	missense_variant	6/12	1	NM_031282.3	ENSP00000271532.1
FCRL4	ENST00000448509.6	n.750C>G		non_coding_transcript_exon_variant	4/9	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.1009C>G (p.Q337E) alteration is located in exon 6 (coding exon 6) of the FCRL4 gene. This alteration results from a C to G substitution at nucleotide position 1009, causing the glutamine (Q) at amino acid position 337 to be replaced by a glutamic acid (E). 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	0.084
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.2
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.066
Sift	Benign	0.12	T
Sift4G	Benign	0.10	T
Polyphen		0.62	P
Vest4		0.17
MutPred		0.42		Loss of MoRF binding (P = 0.025);
MVP		0.33
MPC		0.15
ClinPred		0.83	D
GERP RS		2.3
Varity_R		0.12
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-157556084;