rs6427384

Positions:

• chr1-157539092-C-G
• chr1-157539092-C-T

Variant summary

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

The NM_031281.3(FCRL5):​c.1396G>C​(p.Val466Leu) 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. 13/23 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. V466I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: FCRL5 NM_031281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

Genes affected

FCRL5 (HGNC:18508): (Fc receptor like 5) This gene encodes a member of the immunoglobulin receptor superfamily and the Fc-receptor like family. This gene and several other Fc receptor-like gene members are clustered on the long arm of chromosome 1. The encoded protein is a single-pass type I membrane protein and contains 8 immunoglobulin-like C2-type domains. This gene is implicated in B cell development and lymphomagenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL5	NM_031281.3	c.1396G>C	p.Val466Leu	missense_variant	7/17	ENST00000361835.8	NP_112571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL5	ENST00000361835.8	c.1396G>C	p.Val466Leu	missense_variant	7/17	1	NM_031281.3	ENSP00000354691.3
FCRL5	ENST00000368190.7	c.1396G>C	p.Val466Leu	missense_variant	7/10	1		ENSP00000357173.3
FCRL5	ENST00000368189.3	c.1396G>C	p.Val466Leu	missense_variant	7/8	1		ENSP00000357172.3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.097
DANN	Benign	0.96
DEOGEN2	Benign	0.0027	T;.;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.080	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.013	D;D;D
Sift4G	Benign	0.17	T;T;D
Polyphen		0.82	P;B;D
Vest4		0.37
MutPred		0.48		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.048
MPC		0.090
ClinPred		0.073	T
GERP RS		-1.7
Varity_R		0.23
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: 13

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

Publications

LitVar

Other links and lift over

dbSNP: rs6427384; hg19: chr1-157508882;