1-161727405-C-G

Position:

• chr1-161727405-C-G

Variant summary

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

The ENST00000367948.7(FCRLB):​c.1024C>G​(p.Pro342Ala) 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FCRLB ENST00000367948.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.750

Genes affected

FCRLB (HGNC:26431): (Fc receptor like B) FCRL2 belongs to the Fc receptor family. Fc receptors are involved in phagocytosis, antibody-dependent cell cytotoxicity, immediate hypersensitivity, and transcytosis of immunoglobulins via their ability to bind immunoglobulin (Ig) constant regions (Chikaev et al., 2005 [PubMed 15676285]).[supplied by OMIM, Mar 2008]

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=0.115899086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRLB	NM_001002901.4	c.1024C>G	p.Pro342Ala	missense_variant	8/8	ENST00000367948.7	NP_001002901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRLB	ENST00000367948.7	c.1024C>G	p.Pro342Ala	missense_variant	8/8	1	NM_001002901.4	ENSP00000356925	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2023

The c.1024C>G (p.P342A) alteration is located in exon 6 (coding exon 6) of the FCRLB gene. This alteration results from a C to G substitution at nucleotide position 1024, causing the proline (P) at amino acid position 342 to be replaced by an alanine (A). 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	0.063
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	0.16	D
MutationTaster	Benign	0.95	D;D;D;D;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.037	D
Polyphen		0.36	B
Vest4		0.086
MutPred		0.22		Loss of glycosylation at P342 (P = 0.0673);
MVP		0.57
MPC		0.70
ClinPred		0.26	T
GERP RS		3.3
Varity_R		0.052
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
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

LitVar

Other links and lift over

dbSNP: rs200227833; hg19: chr1-161697195;