10-62085845-T-C
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_032199.3(ARID5B):āc.1343T>Cā(p.Ile448Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
ARID5B
NM_032199.3 missense
NM_032199.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 4.49
Genes affected
ARID5B (HGNC:17362): (AT-rich interaction domain 5B) This gene encodes a member of the AT-rich interaction domain (ARID) family of DNA binding proteins. The encoded protein forms a histone H3K9Me2 demethylase complex with PHD finger protein 2 and regulates the transcription of target genes involved in adipogenesis and liver development. This gene also plays a role in cell growth and differentiation of B-lymphocyte progenitors, and single nucleotide polymorphisms in this gene are associated with acute lymphoblastic leukemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.060153127).
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARID5B | NM_032199.3 | c.1343T>C | p.Ile448Thr | missense_variant | 9/10 | ENST00000279873.12 | |
ARID5B | NM_001244638.2 | c.614T>C | p.Ile205Thr | missense_variant | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARID5B | ENST00000279873.12 | c.1343T>C | p.Ile448Thr | missense_variant | 9/10 | 1 | NM_032199.3 | P3 | |
ARID5B | ENST00000681100.1 | c.1319T>C | p.Ile440Thr | missense_variant | 9/10 | ||||
ARID5B | ENST00000309334.5 | c.614T>C | p.Ile205Thr | missense_variant | 6/7 | 5 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151952Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461714Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727166
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 151952Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74198
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 18, 2021 | The c.1343T>C (p.I448T) alteration is located in exon 9 (coding exon 9) of the ARID5B gene. This alteration results from a T to C substitution at nucleotide position 1343, causing the isoleucine (I) at amino acid position 448 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at