Variant chr19-17403763-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004335.4(BST2):c.475G>C(p.Asp159His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BST2
NM_004335.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.799

Variant links:

Genes affected

BST2 (HGNC:1119): (bone marrow stromal cell antigen 2) Bone marrow stromal cells are involved in the growth and development of B-cells. The specific function of the protein encoded by the bone marrow stromal cell antigen 2 is undetermined; however, this protein may play a role in pre-B-cell growth and in rheumatoid arthritis. [provided by RefSeq, Jul 2008]

BST2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18196106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BST2	NM_004335.4 linkuse as main transcript	c.475G>C	p.Asp159His	missense_variant	4/5	ENST00000252593.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BST2	ENST00000252593.7 linkuse as main transcript	c.475G>C	p.Asp159His	missense_variant	4/5	1	NM_004335.4	P1	Q10589-1
BST2	ENST00000533098.5 linkuse as main transcript	n.290G>C		non_coding_transcript_exon_variant	3/4	2
BST2	ENST00000527220.2 linkuse as main transcript	c.*105G>C		3_prime_UTR_variant, NMD_transcript_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 19, 2023

The c.475G>C (p.D159H) alteration is located in exon 4 (coding exon 4) of the BST2 gene. This alteration results from a G to C substitution at nucleotide position 475, causing the aspartic acid (D) at amino acid position 159 to be replaced by a histidine (H). 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

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.8

DANN

Benign

0.55

DEOGEN2

Benign

0.052

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.71

M_CAP

Benign

0.0030

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.6

REVEL

Benign

0.035

Sift

Benign

0.058

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.099

MutPred

0.17

Gain of catalytic residue at D159 (P = 0.0594);

MVP

0.67

MPC

0.56

ClinPred

0.16

GERP RS

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.041

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over