chr1-157748956-C-T

Variant names:

• chr1-157748956-C-T
• rs745484920
• NM_030764.4:c.1312G>A

Variant summary

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

The NM_030764.4(FCRL2):​c.1312G>A​(p.Ala438Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,378 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A438P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: FCRL2 NM_030764.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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=0.043269217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL2	NM_030764.4	c.1312G>A	p.Ala438Thr	missense_variant	Exon 9 of 12	ENST00000361516.8	NP_110391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL2	ENST00000361516.8	c.1312G>A	p.Ala438Thr	missense_variant	Exon 9 of 12	1	NM_030764.4	ENSP00000355157.3
FCRL2	ENST00000368181.4	c.460G>A	p.Ala154Thr	missense_variant	Exon 6 of 8	1		ENSP00000357163.4
FCRL2	ENST00000368178.3	n.3230G>A		non_coding_transcript_exon_variant	Exon 4 of 7	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 250968 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135654

Gnomad AFR exome AF: 0.00

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: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461378 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727032

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: 0.0000117

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.80
DANN	Benign	0.68
DEOGEN2	Benign	0.0086	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0069	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.060	N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.014
Sift	Benign	0.98	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0020	B;B
Vest4		0.085
MutPred		0.20		Gain of glycosylation at A438 (P = 2e-04);.;
MVP		0.14
MPC		0.036
ClinPred		0.015	T
GERP RS		0.96
Varity_R		0.019
gMVP		0.072

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

Other links and lift over

dbSNP: rs745484920; hg19: chr1-157718746;