rs12036228

Positions:

• chr1-157544301-C-A
• chr1-157544301-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031281.3(FCRL5):​c.805G>T​(p.Val269Phe) 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. 12/21 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. V269I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCRL5 NM_031281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1711013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL5	NM_031281.3	c.805G>T	p.Val269Phe	missense_variant	5/17	ENST00000361835.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL5	ENST00000361835.8	c.805G>T	p.Val269Phe	missense_variant	5/17	1	NM_031281.3	P1
FCRL5	ENST00000368190.7	c.805G>T	p.Val269Phe	missense_variant	5/10	1
FCRL5	ENST00000368189.3	c.805G>T	p.Val269Phe	missense_variant	5/8	1
FCRL5	ENST00000481082.1	n.1003G>T		non_coding_transcript_exon_variant	6/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.49
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;.;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.29	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M;M;M
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.084
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.96	D;P;D
Vest4		0.19
MutPred		0.32		Loss of glycosylation at S268 (P = 0.0885);Loss of glycosylation at S268 (P = 0.0885);Loss of glycosylation at S268 (P = 0.0885);
MVP		0.040
MPC		0.13
ClinPred		0.85	D
GERP RS		-1.6
Varity_R		0.17
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12036228; hg19: chr1-157514091;