NM_001136219.3:c.187C>T

Variant names:

• chr1-161506414-C-T
• rs9427397
• NM_001136219.3:c.187C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001136219.3(FCGR2A):​c.187C>T​(p.Gln63*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,614,092 control chromosomes in the GnomAD database, including 11,453 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.090 (849 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10604 hom.)
• Consequence: FCGR2A NM_001136219.3 stop_gained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.500
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-161506414-C-T is Benign according to our data. Variant chr1-161506414-C-T is described in ClinVar as Benign. ClinVar VariationId is 402852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136219.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2A	NM_001136219.3	MANE Select	c.187C>T	p.Gln63*	stop_gained	Exon 3 of 7	NP_001129691.1	P12318-1
	FCGR2A	NM_021642.5		c.184C>T	p.Gln62*	stop_gained	Exon 3 of 7	NP_067674.2	P12318-2
	FCGR2A	NM_001375296.1		c.187C>T	p.Gln63*	stop_gained	Exon 3 of 6	NP_001362225.1	A0A8V8TPS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2A	ENST00000271450.12	TSL:1 MANE Select	c.187C>T	p.Gln63*	stop_gained	Exon 3 of 7	ENSP00000271450.6	P12318-1
	FCGR2A	ENST00000367972.8	TSL:1	c.184C>T	p.Gln62*	stop_gained	Exon 3 of 7	ENSP00000356949.4	P12318-2
	FCGR2A	ENST00000967690.1		c.187C>T	p.Gln63*	stop_gained	Exon 3 of 8	ENSP00000637749.1

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13645 AN: 152118 Hom.: 847 Cov.: 32

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0847

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.104 AC: 26117 AN: 251418 AF XY: 0.109

Gnomad AFR exome AF: 0.0250

Gnomad AMR exome AF: 0.0637

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.114 AC: 166943 AN: 1461856 Hom.: 10604 Cov.: 32 AF XY: 0.115 AC XY: 83596 AN XY: 727228

African (AFR) AF: 0.0250 AC: 837 AN: 33480

American (AMR) AF: 0.0668 AC: 2986 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6771 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39672

South Asian (SAS) AF: 0.0918 AC: 7921 AN: 86258

European-Finnish (FIN) AF: 0.116 AC: 6194 AN: 53420

Middle Eastern (MID) AF: 0.187 AC: 1077 AN: 5766

European-Non Finnish (NFE) AF: 0.121 AC: 134333 AN: 1112006

Other (OTH) AF: 0.113 AC: 6815 AN: 60394

GnomAD4 genome AF: 0.0896 AC: 13647 AN: 152236 Hom.: 849 Cov.: 32 AF XY: 0.0902 AC XY: 6714 AN XY: 74438

African (AFR) AF: 0.0263 AC: 1095 AN: 41562

American (AMR) AF: 0.0977 AC: 1494 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0848 AC: 409 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1173 AN: 10616

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8275 AN: 67974

Other (OTH) AF: 0.0994 AC: 210 AN: 2112

Alfa AF: 0.101 Hom.: 571

Bravo AF: 0.0888

TwinsUK AF: 0.124 AC: 459

ALSPAC AF: 0.122 AC: 471

ESP6500AA AF: 0.0291 AC: 128

ESP6500EA AF: 0.132 AC: 1131

ExAC AF: 0.103 AC: 12529

Asia WGS AF: 0.0330 AC: 117 AN: 3478

EpiCase AF: 0.142

EpiControl AF: 0.146

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	FCGR2A-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.62
CADD	Pathogenic	28
DANN	Benign	0.81
Eigen	Benign	-0.63
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.022	N
PhyloP100		-0.50
Vest4		0.62
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=185/15	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9427397; hg19: chr1-161476204; COSMIC: COSV107220784; COSMIC: COSV107220784;