GeneBe

NM_007237.5:c.669C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_007237.5(SP140):​c.669C>G​(p.Ser223Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,252 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SP140
NM_007237.5 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

0 publications found
Variant links:
Genes affected
SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 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=-0.88).
BP7
Synonymous conserved (PhyloP=-0.109 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SP140NM_007237.5 linkc.669C>G p.Ser223Ser synonymous_variant Exon 7 of 27 ENST00000392045.8 NP_009168.4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SP140ENST00000392045.8 linkc.669C>G p.Ser223Ser synonymous_variant Exon 7 of 27 2 NM_007237.5 ENSP00000375899.3
SP140ENST00000420434.7 linkc.669C>G p.Ser223Ser synonymous_variant Exon 7 of 26 1 ENSP00000398210.3
SP140ENST00000417495.7 linkc.660C>G p.Ser220Ser synonymous_variant Exon 7 of 24 1 ENSP00000393618.3
SP140ENST00000343805.10 linkc.664+787C>G intron_variant Intron 6 of 24 1 ENSP00000342096.6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1447252
Hom.:
0
Cov.:
28
AF XY:
0.00000139
AC XY:
1
AN XY:
720854
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33248
American (AMR)
AF:
0.00
AC:
0
AN:
44636
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26042
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39660
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85954
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53366
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5736
European-Non Finnish (NFE)
AF:
9.10e-7
AC:
1
AN:
1098708
Other (OTH)
AF:
0.00
AC:
0
AN:
59902
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

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.81
DANN
Benign
0.39
PhyloP100
-0.11
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs28445040; hg19: chr2-231110582; API