1-157578836-C-T

Variant names:

• chr1-157578836-C-T
• NM_031282.3:c.1294G>A

Variant summary

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

The NM_031282.3(FCRL4):​c.1294G>A​(p.Gly432Ser) 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 1,461,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FCRL4 NM_031282.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0380

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]

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=0.14878047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL4	NM_031282.3	c.1294G>A	p.Gly432Ser	missense_variant	Exon 9 of 12	ENST00000271532.2	NP_112572.1
FCRL4	XM_011510034.2	c.1291G>A	p.Gly431Ser	missense_variant	Exon 9 of 12		XP_011508336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL4	ENST00000271532.2	c.1294G>A	p.Gly432Ser	missense_variant	Exon 9 of 12	1	NM_031282.3	ENSP00000271532.1
FCRL4	ENST00000448509.6	n.1035G>A		non_coding_transcript_exon_variant	Exon 7 of 9	2
FCRL4	ENST00000479869.1	n.234G>A		non_coding_transcript_exon_variant	Exon 2 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461102 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726848

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1294G>A (p.G432S) alteration is located in exon 9 (coding exon 9) of the FCRL4 gene. This alteration results from a G to A substitution at nucleotide position 1294, causing the glycine (G) at amino acid position 432 to be replaced by a serine (S). 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	9.5
DANN	Benign	0.95
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.044
Sift	Benign	0.082	T
Sift4G	Benign	0.21	T
Polyphen		0.96	D
Vest4		0.17
MutPred		0.30		Gain of glycosylation at G432 (P = 0.0044);
MVP		0.25
MPC		0.045
ClinPred		0.24	T
GERP RS		-0.48
Varity_R		0.046
gMVP		0.090

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: chr1-157548626;