1-161624537-A-T

Variant names:

• chr1-161624537-A-T
• NM_001244753.2:c.680T>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001244753.2(FCGR3B):​c.680T>A​(p.Phe227Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

Genes affected

FCGR3B (HGNC:3620): (Fc gamma receptor IIIb) The protein encoded by this gene is a low affinity receptor for the Fc region of gamma immunoglobulins (IgG). The encoded protein acts as a monomer and can bind either monomeric or aggregated IgG. This gene may function to capture immune complexes in the peripheral circulation. Several transcript variants encoding different isoforms have been found for this gene. A highly-similar gene encoding a related protein is also found on chromosome 1. [provided by RefSeq, Aug 2012]

ENSG00000289768 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30361292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3B	NM_001244753.2	c.680T>A	p.Phe227Tyr	missense_variant	Exon 5 of 5	ENST00000650385.1	NP_001231682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR3B	ENST00000650385.1	c.680T>A	p.Phe227Tyr	missense_variant	Exon 5 of 5		NM_001244753.2	ENSP00000497461.1
ENSG00000289768	ENST00000699402.1	c.40+6518T>A		intron_variant	Intron 1 of 3			ENSP00000514363.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.680T>A (p.F227Y) alteration is located in exon 6 (coding exon 5) of the FCGR3B gene. This alteration results from a T to A substitution at nucleotide position 680, causing the phenylalanine (F) at amino acid position 227 to be replaced by a tyrosine (Y). 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	0.16
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	.;.;T;.;.;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.043
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.57	.;.;T;T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.30	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.4	.;N;.;.;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.011	.;D;.;.;D;D
Sift4G	Benign	0.26	.;T;T;T;T;T
Vest4		0.30, 0.32, 0.39, 0.29, 0.39
MutPred		0.68		Gain of disorder (P = 0.0844);Gain of disorder (P = 0.0844);.;.;Gain of disorder (P = 0.0844);.;
MVP		0.12
MPC		0.60
ClinPred		0.71	D
GERP RS		3.0
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-161594327;