rs2072243

Positions:

• chr17-14301063-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 17-14301063-C-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 166,954 control chromosomes in the GnomAD database, including 3,757 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 0.20 (3377 hom., cov: 33)
  • Exomes 𝑓: 0.21 (380 hom.)
• Consequence: HS3ST3B1 NM_006041.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

Genes affected

HS3ST3B1 (HGNC:5198): (heparan sulfate-glucosamine 3-sulfotransferase 3B1) The protein encoded by this gene is a type II integral membrane protein that belongs to the 3-O-sulfotransferases family. These proteins catalyze the addition of sulfate groups at the 3-OH position of glucosamine in heparan sulfate. The substrate specificity of individual members of the family is based on prior modification of the heparan sulfate chain, thus allowing different members of the family to generate binding sites for different proteins on the same heparan sulfate chain. Following treatment with a histone deacetylase inhibitor, expression of this gene is activated in a pancreatic cell line. The increased expression results in promotion of the epithelial-mesenchymal transition. In addition, the modification catalyzed by this protein allows herpes simplex virus membrane fusion and penetration. A very closely related homolog with an almost identical sulfotransferase domain maps less than 1 Mb away. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST3B1	NM_006041.3			upstream_gene_variant		ENST00000360954.3	NP_006032.1
HS3ST3B1	NR_130138.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST3B1	ENST00000360954.3			upstream_gene_variant		1	NM_006041.3	ENSP00000354213	P1
HS3ST3B1	ENST00000466596.5			upstream_gene_variant		2		ENSP00000436078

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30907 AN: 152132 Hom.: 3373 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.213 AC: 3138 AN: 14704 Hom.: 380 Cov.: 0 AF XY: 0.220 AC XY: 1650 AN XY: 7504

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.253

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.203 AC: 30926 AN: 152250 Hom.: 3377 Cov.: 33 AF XY: 0.200 AC XY: 14905 AN XY: 74452

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.243

Alfa AF: 0.205 Hom.: 415

Bravo AF: 0.208

Asia WGS AF: 0.258 AC: 898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.5
DANN	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2072243; hg19: chr17-14204380; COSMIC: COSV62906239;