rs3213710

chr4-15715698-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004334.3(BST1):c.612-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,557,570 control chromosomes in the GnomAD database, including 207,443 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (16451 hom., cov: 32)
  • Exomes 𝑓: 0.52 (190992 hom.)
• Consequence: BST1 NM_004334.3 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.001913
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BST1	NM_004334.3	c.612-9G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000265016.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BST1	ENST00000265016.9	c.612-9G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004334.3	P1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67944 AN: 151840 Hom.: 16443 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.473

GnomAD3 exomes AF: 0.518 AC: 118741 AN: 229426 Hom.: 31883 AF XY: 0.523 AC XY: 65017 AN XY: 124324

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.628

Gnomad ASJ exome AF: 0.479

Gnomad EAS exome AF: 0.437

Gnomad SAS exome AF: 0.583

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.519

Gnomad OTH exome AF: 0.520

GnomAD4 exome AF: 0.518 AC: 727548 AN: 1405612 Hom.: 190992 Cov.: 24 AF XY: 0.520 AC XY: 363982 AN XY: 699828

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.614

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.427

Gnomad4 SAS exome AF: 0.583

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.509

GnomAD4 genome AF: 0.447 AC: 67969 AN: 151958 Hom.: 16451 Cov.: 32 AF XY: 0.452 AC XY: 33564 AN XY: 74254

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.431

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.476

Alfa AF: 0.513 Hom.: 34056

Bravo AF: 0.435

Asia WGS AF: 0.496 AC: 1725 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	13
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0019
dbscSNV1_RF	Benign	0.028
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3213710; hg19: chr4-15717321; COSMIC: COSV53947006;