NM_004334.3:c.301A>G

Variant names:

• chr4-15705627-A-G
• rs6840615
• NM_004334.3:c.301A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004334.3(BST1):​c.301A>G​(p.Ile101Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 1,613,918 control chromosomes in the GnomAD database, including 385 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (181 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (204 hom.)
• Consequence: BST1 NM_004334.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.07
• Publications: 12 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022224486).
• BP6: Variant 4-15705627-A-G is Benign according to our data. Variant chr4-15705627-A-G is described in ClinVar as Benign. ClinVar VariationId is 769628.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

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.301A>G	p.Ile101Val	missense	Exon 2 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.301A>G	p.Ile101Val	missense	Exon 2 of 9	ENSP00000265016.4	Q10588-1
	BST1	ENST00000382346.7	TSL:5	c.346A>G	p.Ile116Val	missense	Exon 3 of 10	ENSP00000371783.3	A6NC48
	BST1	ENST00000897441.1		c.301A>G	p.Ile101Val	missense	Exon 2 of 8	ENSP00000567500.1

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4012 AN: 152092 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0922

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.00706 AC: 1774 AN: 251426 AF XY: 0.00517

Gnomad AFR exome AF: 0.0953

Gnomad AMR exome AF: 0.00471

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00300 AC: 4385 AN: 1461708 Hom.: 204 Cov.: 30 AF XY: 0.00263 AC XY: 1915 AN XY: 727184

African (AFR) AF: 0.103 AC: 3457 AN: 33430

American (AMR) AF: 0.00588 AC: 263 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.000232 AC: 20 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5768

European-Non Finnish (NFE) AF: 0.000192 AC: 213 AN: 1111910

Other (OTH) AF: 0.00623 AC: 376 AN: 60392

GnomAD4 genome AF: 0.0264 AC: 4014 AN: 152210 Hom.: 181 Cov.: 32 AF XY: 0.0254 AC XY: 1888 AN XY: 74446

African (AFR) AF: 0.0921 AC: 3821 AN: 41510

American (AMR) AF: 0.00830 AC: 127 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68002

Other (OTH) AF: 0.0166 AC: 35 AN: 2108

Alfa AF: 0.0109 Hom.: 211

Bravo AF: 0.0312

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0878 AC: 387

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00874 AC: 1061

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.86
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.028
Sift	Benign	0.53	T
Sift4G	Benign	0.18	T
Polyphen		0.099	B
Vest4		0.34
MVP		0.27
MPC		0.18
ClinPred		0.0027	T
GERP RS		0.14
Varity_R		0.055
gMVP		0.16
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6840615; hg19: chr4-15707250;