4-15703328-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004334.3(BST1):c.184C>G(p.Gln62Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BST1 NM_004334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.606

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06368905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BST1	NM_004334.3	c.184C>G	p.Gln62Glu	missense_variant	1/9	ENST00000265016.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BST1	ENST00000265016.9	c.184C>G	p.Gln62Glu	missense_variant	1/9	1	NM_004334.3	P1
BST1	ENST00000382346.7	c.184C>G	p.Gln62Glu	missense_variant	1/10	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.184C>G (p.Q62E) alteration is located in exon 1 (coding exon 1) of the BST1 gene. This alteration results from a C to G substitution at nucleotide position 184, causing the glutamine (Q) at amino acid position 62 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	11
Dann	Benign	0.72
DEOGEN2	Benign	0.059	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.44	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.047
Sift	Benign	0.099	T;T
Sift4G	Benign	0.76	T;T
Polyphen		0.0010	B;.
Vest4		0.075
MutPred		0.50		Gain of ubiquitination at K65 (P = 0.0421);Gain of ubiquitination at K65 (P = 0.0421);
MVP		0.19
MPC		0.17
ClinPred		0.064	T
GERP RS		-0.19
Varity_R		0.11
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-15704951;