Variant 1-161591302-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000466542.6(FCGR2C):c.550C>T(p.Pro184Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000554 in 142,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00053 ( 12 hom. )

Failed GnomAD Quality Control

Consequence

FCGR2C
ENST00000466542.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.123

Variant links:

Genes affected

FCGR2C (HGNC:15626): (Fc gamma receptor IIc (gene/pseudogene)) This gene encodes one of three members of a family of low-affinity immunoglobulin gamma Fc receptors found on the surface of many immune response cells. The encoded protein is a transmembrane glycoprotein and may be involved in phagocytosis and clearing of immune complexes. An allelic polymorphism in this gene results in both coding and non-coding variants. [provided by RefSeq, Apr 2012]

FCGR2C links:

ENSG00000289768 (HGNC:):

ENSG00000289768 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047652423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR2C	NR_047648.1 linkuse as main transcript	n.649C>T		non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR2C	ENST00000466542.6 linkuse as main transcript	c.550C>T	p.Pro184Ser	missense_variant	4/7	1		ENSP00000426627.1
ENSG00000289768	ENST00000699402.1 linkuse as main transcript	c.40+39753G>A		intron_variant				ENSP00000514363.1		A0A8V8TN80

Frequencies

GnomAD3 genomes

AF:

0.000555

AC:

AN:

142432

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000207

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00179

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000684

Gnomad OTH

AF:

0.000524

GnomAD3 exomes

AF:

0.000376

AC:

AN:

236894

Hom.:

AF XY:

0.000359

AC XY:

AN XY:

128012

show subpopulations

Gnomad AFR exome

AF:

0.000133

Gnomad AMR exome

AF:

0.000779

Gnomad ASJ exome

AF:

0.000107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000275

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000464

Gnomad OTH exome

AF:

0.000521

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000525

AC:

749

AN:

1426362

Hom.:

Cov.:

AF XY:

0.000575

AC XY:

408

AN XY:

708976

show subpopulations

Gnomad4 AFR exome

AF:

0.0000913

Gnomad4 AMR exome

AF:

0.000775

Gnomad4 ASJ exome

AF:

0.000121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000511

Gnomad4 FIN exome

AF:

0.0000383

Gnomad4 NFE exome

AF:

0.000588

Gnomad4 OTH exome

AF:

0.000390

GnomAD4 genome

AF:

0.000554

AC:

AN:

142542

Hom.:

Cov.:

AF XY:

0.000636

AC XY:

AN XY:

69216

show subpopulations

Gnomad4 AFR

AF:

0.000207

Gnomad4 AMR

AF:

0.00178

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000684

Gnomad4 OTH

AF:

0.000519

Alfa

AF:

0.000532

Hom.:

ExAC

AF:

0.000294

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 27, 2021

The c.550C>T (p.P184S) alteration is located in exon 4 (coding exon 4) of the FCGR2C gene. This alteration results from a C to T substitution at nucleotide position 550, causing the proline (P) at amino acid position 184 to be replaced by a serine (S). 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

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.95

FATHMM_MKL

Benign

0.0084

LIST_S2

Uncertain

0.86

D;D

MetaRNN

Benign

0.048

T;T

Vest4

0.12

MVP

0.27

GERP RS

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over