Variant 1-161591282-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000466542.6(FCGR2C):c.530C>T(p.Ser177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000037 in 1,569,278 control chromosomes in the GnomAD database, including 4 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000071 ( 1 hom., cov: 28)

Exomes 𝑓: 0.000034 ( 3 hom. )

Consequence

FCGR2C
ENST00000466542.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.67

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.062111884).

BP6

Variant 1-161591282-C-T is Benign according to our data. Variant chr1-161591282-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2465865.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 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.629C>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.530C>T	p.Ser177Leu	missense_variant	4/7	1		ENSP00000426627.1
ENSG00000289768	ENST00000699402.1 linkuse as main transcript	c.40+39773G>A		intron_variant				ENSP00000514363.1		A0A8V8TN80

Frequencies

GnomAD3 genomes

AF:

0.0000635

AC:

AN:

141690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000521

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000394

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000530

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

235118

Hom.:

AF XY:

0.0000472

AC XY:

AN XY:

127178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.000137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000956

Gnomad OTH exome

AF:

0.000522

GnomAD4 exome

AF:

0.0000336

AC:

AN:

1427476

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

709424

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000402

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.000107

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.0000111

Gnomad4 OTH exome

AF:

0.000356

GnomAD4 genome

AF:

0.0000705

AC:

AN:

141802

Hom.:

Cov.:

AF XY:

0.0000582

AC XY:

AN XY:

68774

show subpopulations

Gnomad4 AFR

AF:

0.0000780

Gnomad4 AMR

AF:

0.000287

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000395

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000525

Alfa

AF:

0.0000967

Hom.:

ExAC

AF:

0.0000168

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.0010

DANN

Benign

0.71

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.097

T;T

MetaRNN

Benign

0.062

T;T

Vest4

0.12

MVP

0.048

GERP RS

-5.8

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