1-157578836-C-A

Variant names:

• chr1-157578836-C-A
• rs1652479562
• NM_031282.3:c.1294G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031282.3(FCRL4):​c.1294G>T​(p.Gly432Cys) 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. 13/22 in silico tools predict a benign 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. G432S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCRL4 NM_031282.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12140995).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL4	NM_031282.3	MANE Select	c.1294G>T	p.Gly432Cys	missense	Exon 9 of 12	NP_112572.1	Q96PJ5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL4	ENST00000271532.2	TSL:1 MANE Select	c.1294G>T	p.Gly432Cys	missense	Exon 9 of 12	ENSP00000271532.1	Q96PJ5-1
	FCRL4	ENST00000448509.6	TSL:2	n.1035G>T		non_coding_transcript_exon	Exon 7 of 9
	FCRL4	ENST00000479869.1	TSL:3	n.234G>T		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.038
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.020
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.038	D
Polyphen		0.24	B
Vest4		0.28
MutPred		0.26		Loss of sheet (P = 0.0315)
MVP		0.24
MPC		0.040
ClinPred		0.21	T
GERP RS		-0.48
Varity_R		0.16
gMVP		0.11
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1652479562; hg19: chr1-157548626;