17-14311759-A-G

Variant names:

• chr17-14311759-A-G
• rs4791571
• NM_006041.3:c.554+9687A>G

Variant summary

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

The NM_006041.3(HS3ST3B1):​c.554+9687A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,932 control chromosomes in the GnomAD database, including 24,381 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 0.56 (24381 hom., cov: 31)
• Consequence: HS3ST3B1 NM_006041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006041.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	NM_006041.3	MANE Select	c.554+9687A>G		intron	N/A	NP_006032.1
	HS3ST3B1	NR_130138.2		n.992+9687A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST3B1	ENST00000360954.3	TSL:1 MANE Select	c.554+9687A>G		intron	N/A	ENSP00000354213.2
	HS3ST3B1	ENST00000466596.5	TSL:2	n.554+9687A>G		intron	N/A	ENSP00000436078.1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85712 AN: 151816 Hom.: 24359 Cov.: 31

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.717

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.593

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.565 AC: 85780 AN: 151932 Hom.: 24381 Cov.: 31 AF XY: 0.563 AC XY: 41803 AN XY: 74242

African (AFR) AF: 0.533 AC: 22090 AN: 41434

American (AMR) AF: 0.578 AC: 8844 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2318 AN: 3470

East Asian (EAS) AF: 0.640 AC: 3295 AN: 5146

South Asian (SAS) AF: 0.629 AC: 3027 AN: 4810

European-Finnish (FIN) AF: 0.494 AC: 5203 AN: 10540

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.574 AC: 39000 AN: 67932

Other (OTH) AF: 0.595 AC: 1254 AN: 2108

Alfa AF: 0.582 Hom.: 42518

Bravo AF: 0.567

Asia WGS AF: 0.600 AC: 2083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.095
Mutation Taster		=100/0	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: rs4791571; hg19: chr17-14215076; COSMIC: COSV62906250;