1-161549621-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000569.8(FCGR3A):c.40+76G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,563,176 control chromosomes in the GnomAD database, including 106,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (10505 hom., cov: 31)
  • Exomes 𝑓: 0.40 (95509 hom.)
• Consequence: FCGR3A NM_000569.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0870

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-161549621-C-A is Benign according to our data. Variant chr1-161549621-C-A is described in ClinVar as [Benign]. Clinvar id is 2688108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR3A	NM_000569.8	c.40+76G>T		intron_variant		ENST00000443193.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR3A	ENST00000443193.6	c.40+76G>T		intron_variant		1	NM_000569.8	P4

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55506 AN: 151316 Hom.: 10491 Cov.: 31

Gnomad AFR AF: 0.240

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.373

GnomAD4 exome AF: 0.400 AC: 565394 AN: 1411742 Hom.: 95509 AF XY: 0.399 AC XY: 279890 AN XY: 700790

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.407

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.367 AC: 55544 AN: 151434 Hom.: 10505 Cov.: 31 AF XY: 0.367 AC XY: 27168 AN XY: 73984

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.468

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.376

Alfa AF: 0.299 Hom.: 1238

Bravo AF: 0.362

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 53% of patients studied by a panel of primary immunodeficiencies. Number of patients: 50. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.8
Dann	Benign	0.57

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

Other links and lift over

dbSNP: rs10917571; hg19: chr1-161519411;