1-161726774-G-A

Position:

• chr1-161726774-G-A

Variant summary

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

The ENST00000367948.7(FCRLB):​c.646G>A​(p.Val216Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FCRLB ENST00000367948.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0230

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=0.13029015).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRLB	NM_001002901.4	c.646G>A	p.Val216Met	missense_variant	7/8	ENST00000367948.7	NP_001002901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRLB	ENST00000367948.7	c.646G>A	p.Val216Met	missense_variant	7/8	1	NM_001002901.4	ENSP00000356925	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425396 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 706752

Gnomad4 AFR exome AF: 0.0000306

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.: 32

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

Nov 10, 2022

The c.646G>A (p.V216M) alteration is located in exon 5 (coding exon 5) of the FCRLB gene. This alteration results from a G to A substitution at nucleotide position 646, causing the valine (V) at amino acid position 216 to be replaced by a methionine (M). 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	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	M
MutationTaster	Benign	1.0	D;D;D;D;N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.060
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.081	T
Polyphen		0.41	B
Vest4		0.10
MutPred		0.39		Gain of phosphorylation at T221 (P = 0.0857);
MVP		0.21
MPC		0.71
ClinPred		0.64	D
GERP RS		0.91
Varity_R		0.18
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-161696564;