chr1-157767378-C-T

Variant names:

• chr1-157767378-C-T
• rs1649583502
• NM_030764.4:c.1015G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_030764.4(FCRL2):​c.1015G>A​(p.Val339Ile) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FCRL2 NM_030764.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.868

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=0.10449314).
• BP6: Variant 1-157767378-C-T is Benign according to our data. Variant chr1-157767378-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2225982.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL2	NM_030764.4	c.1015G>A	p.Val339Ile	missense_variant	Exon 6 of 12	ENST00000361516.8	NP_110391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL2	ENST00000361516.8	c.1015G>A	p.Val339Ile	missense_variant	Exon 6 of 12	1	NM_030764.4	ENSP00000355157.3
FCRL2	ENST00000469986.1	c.256G>A	p.Val86Ile	missense_variant	Exon 1 of 2	1		ENSP00000417393.1
FCRL2	ENST00000368181.4	c.311-407G>A		intron_variant	Intron 3 of 7	1		ENSP00000357163.4
FCRL2	ENST00000368178.3	n.2933G>A		non_coding_transcript_exon_variant	Exon 1 of 7	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 03, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.5
DANN	Benign	0.67
DEOGEN2	Benign	0.017	T;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.031
Sift	Benign	0.35	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.73	P;.
Vest4		0.13
MutPred		0.32		Loss of glycosylation at S344 (P = 0.2034);.;
MVP		0.13
MPC		0.040
ClinPred		0.49	T
GERP RS		-1.6
Varity_R		0.023
gMVP		0.059

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: rs1649583502; hg19: chr1-157737168;