chr4-15707568-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004334.3(BST1):c.373C>T(p.Arg125Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000545 in 1,614,028 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R125H) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 1 hom. )
Consequence
BST1
NM_004334.3 missense
NM_004334.3 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 4.60
Genes affected
BST1 (HGNC:1118): (bone marrow stromal cell antigen 1) Bone marrow stromal cell antigen-1 is a stromal cell line-derived glycosylphosphatidylinositol-anchored molecule that facilitates pre-B-cell growth. The deduced amino acid sequence exhibits 33% similarity with CD38. BST1 expression is enhanced in bone marrow stromal cell lines derived from patients with rheumatoid arthritis. The polyclonal B-cell abnormalities in rheumatoid arthritis may be, at least in part, attributed to BST1 overexpression in the stromal cell population. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BST1 | NM_004334.3 | c.373C>T | p.Arg125Cys | missense_variant | 3/9 | ENST00000265016.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BST1 | ENST00000265016.9 | c.373C>T | p.Arg125Cys | missense_variant | 3/9 | 1 | NM_004334.3 | P1 | |
BST1 | ENST00000382346.7 | c.418C>T | p.Arg140Cys | missense_variant | 4/10 | 5 | |||
BST1 | ENST00000505785.5 | c.61C>T | p.Arg21Cys | missense_variant | 1/7 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152064Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000596 AC: 15AN: 251490Hom.: 0 AF XY: 0.0000809 AC XY: 11AN XY: 135920
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GnomAD4 exome AF: 0.0000561 AC: 82AN: 1461846Hom.: 1 Cov.: 32 AF XY: 0.0000701 AC XY: 51AN XY: 727222
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74414
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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 | Jul 15, 2021 | The c.373C>T (p.R125C) alteration is located in exon 3 (coding exon 3) of the BST1 gene. This alteration results from a C to T substitution at nucleotide position 373, causing the arginine (R) at amino acid position 125 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of solvent accessibility (P = 0.0674);.;
MVP
MPC
ClinPred
D
GERP RS
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