Genetic Variant FCAR:c.-142T>C (chr19-54874148-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002000.4(FCAR):c.-142T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 890,642 control chromosomes in the GnomAD database, including 106,159 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 0.45 ( 15695 hom., cov: 32)

Exomes 𝑓: 0.49 ( 90464 hom. )

Consequence

FCAR
NM_002000.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.424

Publications

20 publications found

Variant links:

COSMIC-nc: COSV62032303

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCAR	NM_002000.4 link	c.-142T>C		upstream_gene_variant		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.-142T>C		upstream_gene_variant		1	NM_002000.4	ENSP00000347714.3		P24071-1

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68142

AN:

151938

Hom.:

15685

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.377

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.496

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.484

Gnomad OTH

AF:

0.472

GnomAD4 exome

AF:

0.491

AC:

362902

AN:

738584

Hom.:

90464

AF XY:

0.497

AC XY:

190682

AN XY:

383546

show subpopulations

African (AFR)

AF:

0.351

AC:

6465

AN:

18402

American (AMR)

AF:

0.465

AC:

13751

AN:

29578

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

10028

AN:

16600

East Asian (EAS)

AF:

0.389

AC:

13471

AN:

34628

South Asian (SAS)

AF:

0.592

AC:

35142

AN:

59320

European-Finnish (FIN)

AF:

0.504

AC:

24120

AN:

47904

Middle Eastern (MID)

AF:

0.514

AC:

1285

AN:

2500

European-Non Finnish (NFE)

AF:

0.488

AC:

240963

AN:

494228

Other (OTH)

AF:

0.499

AC:

17677

AN:

35424

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

9142

18284

27425

36567

45709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4684

9368

14052

18736

23420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.448

AC:

68189

AN:

152058

Hom.:

15695

Cov.:

AF XY:

0.452

AC XY:

33612

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.350

AC:

14540

AN:

41500

American (AMR)

AF:

0.472

AC:

7214

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.598

AC:

2077

AN:

3472

East Asian (EAS)

AF:

0.376

AC:

1943

AN:

5162

South Asian (SAS)

AF:

0.573

AC:

2764

AN:

4826

European-Finnish (FIN)

AF:

0.496

AC:

5239

AN:

10570

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.484

AC:

32866

AN:

67942

Other (OTH)

AF:

0.478

AC:

1010

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1944

3888

5831

7775

9719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.473

Hom.:

62514

Bravo

AF:

0.439

Asia WGS

AF:

0.523

AC:

1820

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.2

(source)

DANN

Benign

0.26

PhyloP100

-0.42

PromoterAI

0.014

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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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