chr1-161506590-C-T

Variant names:

• chr1-161506590-C-T
• rs151051324
• NM_001136219.3:c.363C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_001136219.3(FCGR2A):​c.363C>T​(p.Ser121Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000833 in 1,613,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00086 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (0 hom.)
• Consequence: FCGR2A NM_001136219.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.0009288
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: -4.62
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-161506590-C-T is Benign according to our data. Variant chr1-161506590-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1284990.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-4.62 with no splicing effect.

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.363C>T	p.Ser121Ser	splice_region synonymous	Exon 3 of 7	NP_001129691.1	P12318-1
	FCGR2A	NM_021642.5		c.360C>T	p.Ser120Ser	splice_region synonymous	Exon 3 of 7	NP_067674.2	P12318-2
	FCGR2A	NM_001375296.1		c.363C>T	p.Ser121Ser	splice_region synonymous	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.363C>T	p.Ser121Ser	splice_region synonymous	Exon 3 of 7	ENSP00000271450.6	P12318-1
	FCGR2A	ENST00000367972.8	TSL:1	c.360C>T	p.Ser120Ser	splice_region synonymous	Exon 3 of 7	ENSP00000356949.4	P12318-2
	FCGR2A	ENST00000699279.1		c.-55C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000514260.1	A0A8V8TN30

Frequencies

GnomAD3 genomes AF: 0.000861 AC: 131 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000820

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.000845 AC: 212 AN: 250944 AF XY: 0.000818

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000830 AC: 1213 AN: 1461638 Hom.: 0 Cov.: 32 AF XY: 0.000853 AC XY: 620 AN XY: 727108

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

African (AFR) AF: 0.00105 AC: 35 AN: 33470

American (AMR) AF: 0.000313 AC: 14 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26134

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39698

South Asian (SAS) AF: 0.000765 AC: 66 AN: 86246

European-Finnish (FIN) AF: 0.000562 AC: 30 AN: 53420

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5766

European-Non Finnish (NFE) AF: 0.000878 AC: 976 AN: 1111818

Other (OTH) AF: 0.000845 AC: 51 AN: 60372

⚠️ 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: 0.000860 AC: 131 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000873 AC XY: 65 AN XY: 74478

African (AFR) AF: 0.000818 AC: 34 AN: 41562

American (AMR) AF: 0.000457 AC: 7 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 68034

Other (OTH) AF: 0.00285 AC: 6 AN: 2108

Alfa AF: 0.000808 Hom.: 0

Bravo AF: 0.000793

EpiCase AF: 0.000818

EpiControl AF: 0.00130

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.85
PhyloP100		-4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00093
dbscSNV1_RF	Benign	0.14
SpliceAI score (max)		0.040		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: rs151051324; hg19: chr1-161476380;