rs7539036

Variant names:

• chr1-161542941-G-A
• rs7539036
• NM_000569.8:c.*71C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000443193.6(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 ENST00000443193.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 17 publications found

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]

FCGR3A Gene-Disease associations (from GenCC):

• autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000273112 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000443193.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3A	NM_000569.8	MANE Select	c.*71C>T		3_prime_UTR	Exon 5 of 5	NP_000560.7
	FCGR3A	NM_001127592.2		c.*71C>T		3_prime_UTR	Exon 5 of 5	NP_001121064.2
	FCGR3A	NM_001329122.1		c.*71C>T		3_prime_UTR	Exon 4 of 4	NP_001316051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3A	ENST00000443193.6	TSL:1 MANE Select	c.*71C>T		3_prime_UTR	Exon 5 of 5	ENSP00000392047.2
	FCGR3A	ENST00000699401.1		c.*193C>T		3_prime_UTR	Exon 6 of 6	ENSP00000514362.1
	FCGR3A	ENST00000699398.1		c.*1548C>T		3_prime_UTR	Exon 5 of 5	ENSP00000514359.1

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

African (AFR) AF: 0.103 AC: 2506 AN: 24286

American (AMR) AF: 0.0587 AC: 1842 AN: 31406

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 1955 AN: 18590

East Asian (EAS) AF: 0.0536 AC: 2007 AN: 37476

South Asian (SAS) AF: 0.172 AC: 10987 AN: 63934

European-Finnish (FIN) AF: 0.0976 AC: 4823 AN: 49430

Middle Eastern (MID) AF: 0.147 AC: 624 AN: 4246

European-Non Finnish (NFE) AF: 0.102 AC: 79834 AN: 782674

Other (OTH) AF: 0.109 AC: 4997 AN: 45830

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

African (AFR) AF: 0.111 AC: 4576 AN: 41270

American (AMR) AF: 0.0712 AC: 1084 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3466

East Asian (EAS) AF: 0.0604 AC: 312 AN: 5162

South Asian (SAS) AF: 0.167 AC: 799 AN: 4792

European-Finnish (FIN) AF: 0.102 AC: 1078 AN: 10528

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7338 AN: 67856

Other (OTH) AF: 0.105 AC: 221 AN: 2100

Alfa AF: 0.104 Hom.: 152

Bravo AF: 0.100

Asia WGS AF: 0.128 AC: 444 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.6
DANN	Benign	0.71
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7539036; hg19: chr1-161512731;