rs2072243

Variant names:

• chr17-14301063-C-T
• rs2072243
• ENST00000725301.1:n.43G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000725301.1(ENSG00000294706):​n.43G>A variant causes a non coding transcript exon 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: ENSG00000294706 ENST00000725301.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 4 publications found

Genes affected

ENSG00000294706 (HGNC:):

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000725301.1. 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
	HS3ST3B1	NM_006041.3	MANE Select	c.-456C>T		upstream_gene	N/A	NP_006032.1
	HS3ST3B1	NR_130138.2		n.-18C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000294706	ENST00000725301.1		n.43G>A		non_coding_transcript_exon	Exon 1 of 1
	HS3ST3B1	ENST00000360954.3	TSL:1 MANE Select	c.-456C>T		upstream_gene	N/A	ENSP00000354213.2
	HS3ST3B1	ENST00000466596.5	TSL:2	n.-456C>T		upstream_gene	N/A	ENSP00000436078.1

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

African (AFR) AF: 0.148 AC: 87 AN: 588

American (AMR) AF: 0.238 AC: 80 AN: 336

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 150 AN: 570

East Asian (EAS) AF: 0.253 AC: 174 AN: 688

South Asian (SAS) AF: 0.227 AC: 107 AN: 472

European-Finnish (FIN) AF: 0.117 AC: 63 AN: 540

Middle Eastern (MID) AF: 0.378 AC: 28 AN: 74

European-Non Finnish (NFE) AF: 0.216 AC: 2249 AN: 10434

Other (OTH) AF: 0.200 AC: 200 AN: 1002

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

African (AFR) AF: 0.138 AC: 5721 AN: 41566

American (AMR) AF: 0.217 AC: 3321 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1056 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1216 AN: 5160

South Asian (SAS) AF: 0.305 AC: 1469 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1388 AN: 10616

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15808 AN: 67996

Other (OTH) AF: 0.243 AC: 513 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.5
DANN	Benign	0.93
PhyloP100		-0.54
PromoterAI		0.044	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

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