NM_001002901.4:c.700T>A

Variant names:

• chr1-161726828-T-A
• NM_001002901.4:c.700T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001002901.4(FCRLB):​c.700T>A​(p.Phe234Ile) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCRLB NM_001002901.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.41
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.84

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.700T>A	p.Phe234Ile	missense	Exon 7 of 8	NP_001002901.1	Q6BAA4-1
	FCRLB	NM_001320241.1		c.700T>A	p.Phe234Ile	missense	Exon 6 of 7	NP_001307170.1	Q6BAA4-1
	FCRLB	NM_001288831.1		c.596T>A	p.Val199Asp	missense	Exon 5 of 6	NP_001275760.1	Q6BAA4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRLB	ENST00000367948.7	TSL:1 MANE Select	c.700T>A	p.Phe234Ile	missense	Exon 7 of 8	ENSP00000356925.2	Q6BAA4-1
	FCRLB	ENST00000336830.9	TSL:1	c.596T>A	p.Val199Asp	missense	Exon 5 of 6	ENSP00000338598.5	Q6BAA4-2
	FCRLB	ENST00000367944.3	TSL:1	c.575T>A	p.Val192Asp	missense	Exon 4 of 5	ENSP00000356921.3	Q6BAA4-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-1.1	T
PhyloP100		2.4
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Pathogenic	0.81
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.023	D
Polyphen		0.65	P
Vest4		0.64
MutPred		0.68		Gain of MoRF binding (P = 0.0926)
MVP		0.93
MPC		1.7
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.68
gMVP		0.51
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

hg19: chr1-161696618;