rs7539036

Positions:

• chr1-161542941-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000569.8(FCGR3A):​c.*71C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,209,478 control chromosomes in the GnomAD database, including 6,909 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (904 hom., cov: 31)
  • Exomes 𝑓: 0.10 (6005 hom.)
• Consequence: FCGR3A NM_000569.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

Genes affected

FCGR3A (HGNC:3619): (Fc gamma receptor IIIa) This gene encodes a receptor for the Fc portion of immunoglobulin G, and it is involved in the removal of antigen-antibody complexes from the circulation, as well as other responses, including antibody dependent cellular mediated cytotoxicity and antibody dependent enhancement of virus infections. This gene (FCGR3A) is highly similar to another nearby gene (FCGR3B) located on chromosome 1. The receptor encoded by this gene is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide, whereas FCGR3B is expressed on polymorphonuclear neutrophils (PMN) where the receptor is anchored through a phosphatidylinositol (PI) linkage. Mutations in this gene are associated with immunodeficiency 20, and have been linked to susceptibility to recurrent viral infections, susceptibility to systemic lupus erythematosus, and alloimmune neonatal neutropenia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

ENSG00000273112 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR3A	NM_000569.8	c.*71C>T		3_prime_UTR_variant	5/5	ENST00000443193.6	NP_000560.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR3A	ENST00000443193	c.*71C>T		3_prime_UTR_variant	5/5	1	NM_000569.8	ENSP00000392047.2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15897 AN: 151490 Hom.: 897 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0714

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.104 AC: 109575 AN: 1057872 Hom.: 6005 Cov.: 13 AF XY: 0.106 AC XY: 56712 AN XY: 533492

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0587

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.0536

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.0976

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.109

GnomAD4 genome AF: 0.105 AC: 15926 AN: 151606 Hom.: 904 Cov.: 31 AF XY: 0.106 AC XY: 7823 AN XY: 74102

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0712

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.0604

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.105

Alfa AF: 0.105 Hom.: 146

Bravo AF: 0.100

Asia WGS AF: 0.128 AC: 444 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs7539036; hg19: chr1-161512731;