1-161726801-C-A

Variant names:

• chr1-161726801-C-A
• rs780542339
• NM_001002901.4:c.673C>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.673C>A​(p.Pro225Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000709 in 1,411,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P225S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FCRLB NM_001002901.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• 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, 0.791

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.673C>A	p.Pro225Thr	missense	Exon 7 of 8	NP_001002901.1	Q6BAA4-1
	FCRLB	NM_001320241.1		c.673C>A	p.Pro225Thr	missense	Exon 6 of 7	NP_001307170.1	Q6BAA4-1
	FCRLB	NM_001288829.1		c.575-47C>A		intron	N/A	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.673C>A	p.Pro225Thr	missense	Exon 7 of 8	ENSP00000356925.2	Q6BAA4-1
	FCRLB	ENST00000367946.7	TSL:1	c.575-47C>A		intron	N/A	ENSP00000356923.3	Q6BAA4-4
	FCRLB	ENST00000367945.5	TSL:1	c.554-47C>A		intron	N/A	ENSP00000356922.1	Q6BAA4-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000609 AC: 1 AN: 164274 AF XY: 0.0000110

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1411402 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 698110

African (AFR) AF: 0.00 AC: 0 AN: 32108

American (AMR) AF: 0.00 AC: 0 AN: 37838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24326

East Asian (EAS) AF: 0.00 AC: 0 AN: 37520

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79894

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4700

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088348

Other (OTH) AF: 0.00 AC: 0 AN: 58198

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000861 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.58	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.59
Sift	Benign	0.28	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.58
MutPred		0.32		Gain of MoRF binding (P = 0.0572)
MVP		0.87
MPC		1.8
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.45
gMVP		0.48
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs780542339; hg19: chr1-161696591;