Variant 1-161591360-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000466542.6(FCGR2C):c.608C>T(p.Thr203Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00362 in 143,792 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 28)

Exomes 𝑓: 0.0021 ( 36 hom. )

Failed GnomAD Quality Control

Consequence

FCGR2C
ENST00000466542.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.62

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01078552).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR2C	NR_047648.1 linkuse as main transcript	n.707C>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.608C>T	p.Thr203Met	missense_variant	4/7	1		ENSP00000426627.1
ENSG00000289768	ENST00000699402.1 linkuse as main transcript	c.40+39695G>A		intron_variant				ENSP00000514363.1		A0A8V8TN80

Frequencies

GnomAD3 genomes

AF:

0.00361

AC:

519

AN:

143678

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00213

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00244

Gnomad FIN

AF:

0.00592

Gnomad MID

AF:

0.00329

Gnomad NFE

AF:

0.00532

Gnomad OTH

AF:

0.00511

GnomAD3 exomes

AF:

0.00171

AC:

404

AN:

236682

Hom.:

AF XY:

0.00176

AC XY:

225

AN XY:

127756

show subpopulations

Gnomad AFR exome

AF:

0.000452

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00153

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00103

Gnomad NFE exome

AF:

0.00217

Gnomad OTH exome

AF:

0.00208

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00208

AC:

2935

AN:

1411696

Hom.:

Cov.:

AF XY:

0.00221

AC XY:

1549

AN XY:

701746

show subpopulations

Gnomad4 AFR exome

AF:

0.000519

Gnomad4 AMR exome

AF:

0.00214

Gnomad4 ASJ exome

AF:

0.00200

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00228

Gnomad4 FIN exome

AF:

0.00462

Gnomad4 NFE exome

AF:

0.00206

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.00362

AC:

520

AN:

143792

Hom.:

Cov.:

AF XY:

0.00331

AC XY:

232

AN XY:

70018

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00295

Gnomad4 ASJ

AF:

0.00213

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00244

Gnomad4 FIN

AF:

0.00592

Gnomad4 NFE

AF:

0.00532

Gnomad4 OTH

AF:

0.00506

Alfa

AF:

0.00454

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000360

AC:

ExAC

AF:

0.000625

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

Sep 27, 2022

The c.608C>T (p.T203M) 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 608, causing the threonine (T) at amino acid position 203 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

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

0.0010

DANN

Benign

0.78

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.011

T;T

Vest4

0.14

MVP

0.076

GERP RS

-5.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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