1-161518174-T-C

Variant names:

• chr1-161518174-T-C
• rs13878
• NM_001136219.3:c.*26T>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001136219.3(FCGR2A):​c.*26T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00821 in 1,573,036 control chromosomes in the GnomAD database, including 1,082 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 0.014 (112 hom., cov: 33)
  • Exomes 𝑓: 0.0076 (970 hom.)
• Consequence: FCGR2A NM_001136219.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• Publications: 4 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]

ENSG00000273112 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS2: High Homozygotes in GnomAd4 at 112 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2A	NM_001136219.3	MANE Select	c.*26T>C		3_prime_UTR	Exon 7 of 7	NP_001129691.1
	FCGR2A	NM_021642.5		c.*26T>C		3_prime_UTR	Exon 7 of 7	NP_067674.2
	FCGR2A	NM_001375296.1		c.*26T>C		3_prime_UTR	Exon 6 of 6	NP_001362225.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2A	ENST00000271450.12	TSL:1 MANE Select	c.*26T>C		3_prime_UTR	Exon 7 of 7	ENSP00000271450.6
	FCGR2A	ENST00000367972.8	TSL:1	c.*26T>C		3_prime_UTR	Exon 7 of 7	ENSP00000356949.4
	FCGR2A	ENST00000461298.1	TSL:2	n.389T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 2039 AN: 140728 Hom.: 111 Cov.: 33

Gnomad AFR AF: 0.00943

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.00649

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.00276

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000952

Gnomad OTH AF: 0.0133

GnomAD2 exomes AF: 0.0141 AC: 3379 AN: 239142 AF XY: 0.0139

Gnomad AFR exome AF: 0.00356

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.00187

Gnomad EAS exome AF: 0.142

Gnomad FIN exome AF: 0.00121

Gnomad NFE exome AF: 0.000180

Gnomad OTH exome AF: 0.00867

GnomAD4 exome AF: 0.00760 AC: 10878 AN: 1432184 Hom.: 970 Cov.: 31 AF XY: 0.00856 AC XY: 6091 AN XY: 711274

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00326 AC: 106 AN: 32528

American (AMR) AF: 0.0123 AC: 516 AN: 42004

Ashkenazi Jewish (ASJ) AF: 0.00295 AC: 74 AN: 25110

East Asian (EAS) AF: 0.191 AC: 7135 AN: 37282

South Asian (SAS) AF: 0.0295 AC: 2430 AN: 82234

European-Finnish (FIN) AF: 0.00122 AC: 64 AN: 52310

Middle Eastern (MID) AF: 0.000534 AC: 3 AN: 5622

European-Non Finnish (NFE) AF: 0.000183 AC: 201 AN: 1096438

Other (OTH) AF: 0.00595 AC: 349 AN: 58656

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0145 AC: 2036 AN: 140852 Hom.: 112 Cov.: 33 AF XY: 0.0168 AC XY: 1155 AN XY: 68774

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00938 AC: 367 AN: 39144

American (AMR) AF: 0.0195 AC: 269 AN: 13784

Ashkenazi Jewish (ASJ) AF: 0.00649 AC: 21 AN: 3234

East Asian (EAS) AF: 0.212 AC: 1007 AN: 4744

South Asian (SAS) AF: 0.0621 AC: 259 AN: 4174

European-Finnish (FIN) AF: 0.00276 AC: 27 AN: 9774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.000952 AC: 60 AN: 63030

Other (OTH) AF: 0.0137 AC: 26 AN: 1896

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00675 Hom.: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.6
DANN	Benign	0.83
PhyloP100		-0.97
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs13878; hg19: chr1-161487964;