Genetic Variant NM_002000.4:c.324G>A (chr19-54885488-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002000.4(FCAR):c.324G>A(p.Arg108Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,096 control chromosomes in the GnomAD database, including 67,793 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 0.26 ( 5811 hom., cov: 31)

Exomes 𝑓: 0.29 ( 61982 hom. )

Consequence

FCAR
NM_002000.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.78

Publications

23 publications found

Variant links:

Genes affected

FCAR (HGNC:3608): (Fc alpha receptor) This gene is a member of the immunoglobulin gene superfamily and encodes a receptor for the Fc region of IgA. The receptor is a transmembrane glycoprotein present on the surface of myeloid lineage cells such as neutrophils, monocytes, macrophages, and eosinophils, where it mediates immunologic responses to pathogens. It interacts with IgA-opsonized targets and triggers several immunologic defense processes, including phagocytosis, antibody-dependent cell-mediated cytotoxicity, and stimulation of the release of inflammatory mediators. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

FCAR links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP7

Synonymous conserved (PhyloP=1.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCAR	NM_002000.4 link	c.324G>A	p.Arg108Arg	synonymous_variant	Exon 3 of 5	ENST00000355524.8	NP_001991.1	P24071-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCAR	ENST00000355524.8 link	c.324G>A	p.Arg108Arg	synonymous_variant	Exon 3 of 5	1	NM_002000.4	ENSP00000347714.3		P24071-1

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39758

AN:

151942

Hom.:

5802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.348

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.289

GnomAD4 exome

AF:

0.286

AC:

418334

AN:

1461036

Hom.:

61982

Cov.:

AF XY:

0.288

AC XY:

209233

AN XY:

726850

show subpopulations

African (AFR)

AF:

0.132

AC:

4418

AN:

33468

American (AMR)

AF:

0.478

AC:

21350

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

6945

AN:

26128

East Asian (EAS)

AF:

0.291

AC:

11537

AN:

39700

South Asian (SAS)

AF:

0.347

AC:

29895

AN:

86234

European-Finnish (FIN)

AF:

0.343

AC:

18337

AN:

53410

Middle Eastern (MID)

AF:

0.241

AC:

1387

AN:

5766

European-Non Finnish (NFE)

AF:

0.277

AC:

307334

AN:

1111256

Other (OTH)

AF:

0.284

AC:

17131

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

16065

32131

48196

64262

80327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.262

AC:

39782

AN:

152060

Hom.:

5811

Cov.:

AF XY:

0.271

AC XY:

20156

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.141

AC:

5834

AN:

41504

American (AMR)

AF:

0.410

AC:

6263

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

915

AN:

3466

East Asian (EAS)

AF:

0.265

AC:

1369

AN:

5172

South Asian (SAS)

AF:

0.348

AC:

1674

AN:

4812

European-Finnish (FIN)

AF:

0.351

AC:

3713

AN:

10572

Middle Eastern (MID)

AF:

0.175

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.282

AC:

19160

AN:

67954

Other (OTH)

AF:

0.292

AC:

618

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1479

2958

4437

5916

7395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.269

Hom.:

10125

Bravo

AF:

0.257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.8

(source)

PhyloP100

1.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_002000.4:c.324G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over