NM_052939.4:c.1956T>C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_052939.4(FCRL3):c.1956T>C(p.Asn652Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,578,896 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 7.0e-7 ( 0 hom. )
Consequence
FCRL3
NM_052939.4 splice_region, synonymous
NM_052939.4 splice_region, synonymous
Scores
2
Splicing: ADA: 0.00001921
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.490
Publications
0 publications found
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]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP7
Synonymous conserved (PhyloP=-0.49 with no splicing effect.
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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FCRL3 | MANE Select | c.1956T>C | p.Asn652Asn | splice_region synonymous | Exon 12 of 15 | NP_443171.2 | |||
| FCRL3 | c.1956T>C | p.Asn652Asn | splice_region synonymous | Exon 12 of 16 | NP_001307262.1 | Q96P31-6 | |||
| FCRL3 | n.2178T>C | splice_region non_coding_transcript_exon | Exon 12 of 16 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FCRL3 | TSL:1 MANE Select | c.1956T>C | p.Asn652Asn | splice_region synonymous | Exon 12 of 15 | ENSP00000357167.3 | Q96P31-1 | ||
| FCRL3 | TSL:1 | c.1956T>C | p.Asn652Asn | splice_region synonymous | Exon 12 of 16 | ENSP00000357169.5 | Q96P31-6 | ||
| FCRL3 | TSL:1 | n.2798T>C | splice_region non_coding_transcript_exon | Exon 6 of 9 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151976Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151976
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 7.01e-7 AC: 1AN: 1426920Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1AN XY: 707822 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1426920
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
707822
show subpopulations
African (AFR)
AF:
AC:
0
AN:
32056
American (AMR)
AF:
AC:
0
AN:
37782
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23444
East Asian (EAS)
AF:
AC:
0
AN:
39568
South Asian (SAS)
AF:
AC:
1
AN:
78592
European-Finnish (FIN)
AF:
AC:
0
AN:
52196
Middle Eastern (MID)
AF:
AC:
0
AN:
5562
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1098806
Other (OTH)
AF:
AC:
0
AN:
58914
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000658 AC: 1AN: 151976Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74236 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
151976
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74236
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
41376
American (AMR)
AF:
AC:
1
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5166
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10582
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67978
Other (OTH)
AF:
AC:
0
AN:
2090
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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