chr4-15703224-C-T

Variant names:

• chr4-15703224-C-T
• rs781454882
• NM_004334.3:c.80C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004334.3(BST1):​c.80C>T​(p.Ala27Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000343 in 1,546,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: BST1 NM_004334.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.51
• Publications: 1 publications found

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]

ENSG00000288606 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039208382).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BST1	NM_004334.3	MANE Select	c.80C>T	p.Ala27Val	missense	Exon 1 of 9	NP_004325.2	Q10588-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BST1	ENST00000265016.9	TSL:1 MANE Select	c.80C>T	p.Ala27Val	missense	Exon 1 of 9	ENSP00000265016.4	Q10588-1
	BST1	ENST00000382346.7	TSL:5	c.80C>T	p.Ala27Val	missense	Exon 1 of 10	ENSP00000371783.3	A6NC48
	BST1	ENST00000897441.1		c.80C>T	p.Ala27Val	missense	Exon 1 of 8	ENSP00000567500.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000140 AC: 2 AN: 142588 AF XY: 0.0000128

Gnomad AFR exome AF: 0.000154

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000323 AC: 45 AN: 1394334 Hom.: 0 Cov.: 31 AF XY: 0.0000291 AC XY: 20 AN XY: 688156

African (AFR) AF: 0.0000318 AC: 1 AN: 31460

American (AMR) AF: 0.0000283 AC: 1 AN: 35348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25010

East Asian (EAS) AF: 0.00 AC: 0 AN: 35628

South Asian (SAS) AF: 0.00 AC: 0 AN: 79498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5222

European-Non Finnish (NFE) AF: 0.0000389 AC: 42 AN: 1079410

Other (OTH) AF: 0.0000173 AC: 1 AN: 57846

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74304

African (AFR) AF: 0.0000724 AC: 3 AN: 41450

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000298 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000192 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.9
DANN	Benign	0.92
DEOGEN2	Benign	0.081	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.5
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.011
Sift	Benign	0.35	T
Sift4G	Benign	0.084	T
Polyphen		0.26	B
Vest4		0.14
MVP		0.18
MPC		0.16
ClinPred		0.062	T
GERP RS		-1.0
PromoterAI		-0.012	Neutral
Varity_R		0.023
gMVP		0.29
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs781454882; hg19: chr4-15704847; COSMIC: COSV105872360; COSMIC: COSV105872360;