1-157746873-T-G

Variant names:

• chr1-157746873-T-G
• NM_030764.4:c.1486A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030764.4(FCRL2):​c.1486A>C​(p.Lys496Gln) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCRL2 NM_030764.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001173
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.168

Genes affected

FCRL2 (HGNC:14875): (Fc receptor like 2) 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 one immunoreceptor-tyrosine activation motif and two immunoreceptor-tyrosine inhibitory motifs. This protein may be a prognostic marker for chronic lymphocytic leukemia. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066967785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL2	NM_030764.4	c.1486A>C	p.Lys496Gln	missense_variant, splice_region_variant	Exon 11 of 12	ENST00000361516.8	NP_110391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL2	ENST00000361516.8	c.1486A>C	p.Lys496Gln	missense_variant, splice_region_variant	Exon 11 of 12	1	NM_030764.4	ENSP00000355157.3
FCRL2	ENST00000368181.4	c.568A>C	p.Lys190Gln	missense_variant, splice_region_variant	Exon 7 of 8	1		ENSP00000357163.4
FCRL2	ENST00000368178.3	n.3404A>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 6 of 7	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1486A>C (p.K496Q) alteration is located in exon 11 (coding exon 11) of the FCRL2 gene. This alteration results from a A to C substitution at nucleotide position 1486, causing the lysine (K) at amino acid position 496 to be replaced by a glutamine (Q). 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	0.099
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	11
DANN	Benign	0.90
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.017
Sift	Benign	0.063	T;T
Sift4G	Benign	0.20	T;D
Polyphen		0.24	B;D
Vest4		0.17
MutPred		0.40		Loss of ubiquitination at K496 (P = 0.0051);.;
MVP		0.17
MPC		0.041
ClinPred		0.15	T
GERP RS		1.1
Varity_R		0.088
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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: chr1-157716663;