Variant 1-161589571-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.143C>T(p.Pro48Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000566 in 1,554,492 control chromosomes in the GnomAD database, including 7 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P48T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00029 ( 3 hom., cov: 28)

Exomes 𝑓: 0.000033 ( 4 hom. )

Consequence

FCGR2C
ENST00000466542.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.053287923).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR2C	NR_047648.1 linkuse as main transcript	n.242C>T		non_coding_transcript_exon_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR2C	ENST00000466542.6 linkuse as main transcript	c.143C>T	p.Pro48Leu	missense_variant	3/7	1		ENSP00000426627.1
ENSG00000289768	ENST00000699402.1 linkuse as main transcript	c.41-40540G>A		intron_variant				ENSP00000514363.1		A0A8V8TN80

Frequencies

GnomAD3 genomes

AF:

0.000293

AC:

AN:

143480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000924

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000141

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000665

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000520

GnomAD3 exomes

AF:

0.0000826

AC:

AN:

242112

Hom.:

AF XY:

0.0000994

AC XY:

AN XY:

130804

show subpopulations

Gnomad AFR exome

AF:

0.000954

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000326

AC:

AN:

1410892

Hom.:

Cov.:

AF XY:

0.0000356

AC XY:

AN XY:

701478

show subpopulations

Gnomad4 AFR exome

AF:

0.000615

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000250

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000686

GnomAD4 genome

AF:

0.000292

AC:

AN:

143600

Hom.:

Cov.:

AF XY:

0.000300

AC XY:

AN XY:

69946

show subpopulations

Gnomad4 AFR

AF:

0.000921

Gnomad4 AMR

AF:

0.000140

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000665

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000514

Alfa

AF:

0.0000289

Hom.:

ESP6500AA

AF:

0.00209

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000135

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 14, 2021

The c.143C>T (p.P48L) alteration is located in exon 3 (coding exon 3) of the FCGR2C gene. This alteration results from a C to T substitution at nucleotide position 143, causing the proline (P) at amino acid position 48 to be replaced by a leucine (L). 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

-0.32

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.79

T;T

MetaRNN

Benign

0.053

T;T

Vest4

0.52

MVP

0.52

GERP RS

2.3

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