Genetic Variant FCRL3:c.1412-1525G>C (chr1-157692058-C-G) – 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.1412-1525G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,970 control chromosomes in the GnomAD database, including 29,599 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 0.60 ( 29597 hom., cov: 31)

Exomes 𝑓: 0.43 ( 2 hom. )

Consequence

FCRL3
NM_052939.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0340

Publications

21 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:

FCRL3-AS1 (HGNC:40842):

FCRL3-AS1 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=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 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.1412-1525G>C	intron	N/A	NP_443171.2
FCRL3	NM_001320333.2		c.1412-1525G>C	intron	N/A	NP_001307262.1	Q96P31-6
FCRL3	NR_135214.2		n.1634-1525G>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCRL3	ENST00000368184.8	TSL:1 MANE Select	c.1412-1525G>C	intron	N/A	ENSP00000357167.3	Q96P31-1
FCRL3	ENST00000368186.9	TSL:1	c.1412-1525G>C	intron	N/A	ENSP00000357169.5	Q96P31-6
FCRL3	ENST00000473231.5	TSL:1	n.2254-1525G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.597

AC:

90715

AN:

151838

Hom.:

29540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.516

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.572

GnomAD4 exome

AF:

0.429

AC:

AN:

Hom.:

Cov.:

AF XY:

0.400

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.598

AC:

90820

AN:

151956

Hom.:

29597

Cov.:

AF XY:

0.589

AC XY:

43719

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.883

AC:

36618

AN:

41468

American (AMR)

AF:

0.516

AC:

7877

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

1803

AN:

3472

East Asian (EAS)

AF:

0.413

AC:

2132

AN:

5164

South Asian (SAS)

AF:

0.379

AC:

1822

AN:

4806

European-Finnish (FIN)

AF:

0.458

AC:

4825

AN:

10526

Middle Eastern (MID)

AF:

0.568

AC:

167

AN:

294

European-Non Finnish (NFE)

AF:

0.499

AC:

33867

AN:

67926

Other (OTH)

AF:

0.573

AC:

1210

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1615

3231

4846

6462

8077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.380

Hom.:

1020

Bravo

AF:

0.618

Asia WGS

AF:

0.464

AC:

1613

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.0

(source)

DANN

Benign

0.34

PhyloP100

-0.034

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over