1-161509809-G-A

Variant summary

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

The NM_001136219.3(FCGR2A):c.365-11G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,708 control chromosomes in the GnomAD database, including 11,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.098 (915 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10716 hom.)
• Consequence: FCGR2A NM_001136219.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001120
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.353

Genes affected

FCGR2A (HGNC:3616): (Fc gamma receptor IIa) This gene encodes one member of a family of immunoglobulin Fc receptor genes found on the surface of many immune response cells. The protein encoded by this gene is a cell surface receptor found on phagocytic cells such as macrophages and neutrophils, and is involved in the process of phagocytosis and clearing of immune complexes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 1-161509809-G-A is Benign according to our data. Variant chr1-161509809-G-A is described in ClinVar as [Benign]. Clinvar id is 402853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR2A	NM_001136219.3	c.365-11G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000271450.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR2A	ENST00000271450.12	c.365-11G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001136219.3	A2

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14913 AN: 152032 Hom.: 913 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0852

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.110

GnomAD3 exomes AF: 0.106 AC: 26746 AN: 251380 Hom.: 1853 AF XY: 0.111 AC XY: 15036 AN XY: 135866

Gnomad AFR exome AF: 0.0522

Gnomad AMR exome AF: 0.0668

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0888

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.115 AC: 168579 AN: 1461558 Hom.: 10716 Cov.: 32 AF XY: 0.116 AC XY: 84306 AN XY: 727094

Gnomad4 AFR exome AF: 0.0501

Gnomad4 AMR exome AF: 0.0700

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0918

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.0980 AC: 14914 AN: 152150 Hom.: 915 Cov.: 32 AF XY: 0.0986 AC XY: 7332 AN XY: 74372

Gnomad4 AFR AF: 0.0525

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0851

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.110

Alfa AF: 0.135 Hom.: 1569

Bravo AF: 0.0984

Asia WGS AF: 0.0350 AC: 123 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

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	2.4
Dann	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.0040
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: rs7529425; hg19: chr1-161479599;