rs1231208478

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-161725887-G-A
• chr1-161725887-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002901.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRLB	NM_001002901.4	MANE Select	c.374G>A	p.Arg125His	missense	Exon 6 of 8	NP_001002901.1	Q6BAA4-1
	FCRLB	NM_001320241.1		c.374G>A	p.Arg125His	missense	Exon 5 of 7	NP_001307170.1	Q6BAA4-1
	FCRLB	NM_001288829.1		c.374G>A	p.Arg125His	missense	Exon 4 of 6	NP_001275758.1	Q6BAA4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRLB	ENST00000367948.7	TSL:1 MANE Select	c.374G>A	p.Arg125His	missense	Exon 6 of 8	ENSP00000356925.2	Q6BAA4-1
	FCRLB	ENST00000367946.7	TSL:1	c.374G>A	p.Arg125His	missense	Exon 4 of 6	ENSP00000356923.3	Q6BAA4-4
	FCRLB	ENST00000367945.5	TSL:1	c.353G>A	p.Arg118His	missense	Exon 3 of 5	ENSP00000356922.1	Q6BAA4-5

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

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.10	N
PhyloP100		4.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.23
Sift	Benign	0.50	T
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.64
MutPred		0.62		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
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1231208478; hg19: chr1-161695677;