1-161725887-G-A

Variant names:

• chr1-161725887-G-A
• rs1231208478
• NM_001002901.4:c.374G>A

Variant summary

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

The NM_001002901.4(FCRLB):​c.374G>A​(p.Arg125His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FCRLB NM_001002901.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRLB	NM_001002901.4	c.374G>A	p.Arg125His	missense_variant	Exon 6 of 8	ENST00000367948.7	NP_001002901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRLB	ENST00000367948.7	c.374G>A	p.Arg125His	missense_variant	Exon 6 of 8	1	NM_001002901.4	ENSP00000356925.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461870 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727234

Gnomad4 AFR exome AF: 0.0000597

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.374G>A (p.R125H) alteration is located in exon 4 (coding exon 4) of the FCRLB gene. This alteration results from a G to A substitution at nucleotide position 374, causing the arginine (R) at amino acid position 125 to be replaced by a histidine (H). 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	0.18
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;.;.;.;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.58	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.10	N;N;.;N;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.39	N;N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.50	T;T;T;T;T
Sift4G	Benign	0.19	T;T;D;T;T
Polyphen		1.0	D;D;D;D;D
Vest4		0.64
MutPred		0.62		Loss of MoRF binding (P = 0.0578);Loss of MoRF binding (P = 0.0578);.;Loss of MoRF binding (P = 0.0578);.;
MVP		0.47
MPC		1.9
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.18
gMVP		0.39

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: rs1231208478; hg19: chr1-161695677;