dbSNP rs11264799: FCRL3:c.-402G>A (chr1-157700967-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_052939.4(FCRL3):c.-402G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 161,554 control chromosomes in the GnomAD database, including 6,288 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 0.28 ( 6101 hom., cov: 32)

Exomes 𝑓: 0.19 ( 187 hom. )

Consequence

FCRL3
NM_052939.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.849

Publications

35 publications found

Variant links:

Genes affected

FCRL3 (HGNC:18506): (Fc receptor like 3) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein contains immunoreceptor-tyrosine activation motifs and immunoreceptor-tyrosine inhibitory motifs in its cytoplasmic domain and may play a role in regulation of the immune system. Mutations in this gene have been associated with rheumatoid arthritis, autoimmune thyroid disease, and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

FCRL3 links:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052939.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCRL3	NM_052939.4	MANE Select	c.-402G>A	upstream_gene	N/A	NP_443171.2
FCRL3	NM_001320333.2		c.-402G>A	upstream_gene	N/A	NP_001307262.1	Q96P31-6
FCRL3	NR_135214.2		n.-198G>A	upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCRL3	ENST00000368184.8	TSL:1 MANE Select	c.-402G>A	upstream_gene	N/A	ENSP00000357167.3	Q96P31-1
FCRL3	ENST00000368186.9	TSL:1	c.-402G>A	upstream_gene	N/A	ENSP00000357169.5	Q96P31-6
FCRL3	ENST00000477837.5	TSL:1	n.-402G>A	upstream_gene	N/A	ENSP00000433430.1	Q96P31-2

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42741

AN:

151890

Hom.:

6094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.285

GnomAD4 exome

AF:

0.192

AC:

1831

AN:

9546

Hom.:

187

AF XY:

0.194

AC XY:

943

AN XY:

4862

show subpopulations

African (AFR)

AF:

0.361

AC:

AN:

194

American (AMR)

AF:

0.185

AC:

269

AN:

1454

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

AN:

172

East Asian (EAS)

AF:

0.142

AC:

AN:

600

South Asian (SAS)

AF:

0.123

AC:

102

AN:

828

European-Finnish (FIN)

AF:

0.129

AC:

AN:

132

Middle Eastern (MID)

AF:

0.214

AC:

AN:

European-Non Finnish (NFE)

AF:

0.205

AC:

1180

AN:

5746

Other (OTH)

AF:

0.191

AC:

AN:

392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

145

217

290

362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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:

0.281

AC:

42773

AN:

152008

Hom.:

6101

Cov.:

AF XY:

0.278

AC XY:

20676

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.351

AC:

14561

AN:

41446

American (AMR)

AF:

0.268

AC:

4088

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

904

AN:

3466

East Asian (EAS)

AF:

0.232

AC:

1196

AN:

5166

South Asian (SAS)

AF:

0.183

AC:

883

AN:

4812

European-Finnish (FIN)

AF:

0.237

AC:

2497

AN:

10552

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.260

AC:

17684

AN:

67986

Other (OTH)

AF:

0.290

AC:

610

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1564

3129

4693

6258

7822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.270

Hom.:

2406

Bravo

AF:

0.289

Asia WGS

AF:

0.269

AC:

934

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.6

(source)

DANN

Benign

0.72

PhyloP100

-0.85

PromoterAI

-0.033

Neutral

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over