rs8049738

Positions:

• chr16-25958711-T-C
• chr16-25958711-T-G

Variant summary

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

The NM_006040.3(HS3ST4):​c.735-176901T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 152,164 control chromosomes in the GnomAD database, including 51,372 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 0.82 (51372 hom., cov: 31)
• Consequence: HS3ST4 NM_006040.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

Genes affected

HS3ST4 (HGNC:5200): (heparan sulfate-glucosamine 3-sulfotransferase 4) This gene encodes the enzyme heparan sulfate D-glucosaminyl 3-O-sulfotransferase 4. This enzyme generates 3-O-sulfated glucosaminyl residues in heparan sulfate. Cell surface heparan sulfate is used as a receptor by herpes simplex virus type 1 (HSV-1), and expression of this gene is thought to play a role in HSV-1 pathogenesis. [provided by RefSeq, Jul 2008]

HS3ST4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST4	NM_006040.3	c.735-176901T>C		intron_variant		ENST00000331351.6	NP_006031.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST4	ENST00000331351.6	c.735-176901T>C		intron_variant		1	NM_006040.3	ENSP00000330606.5
HS3ST4	ENST00000475436.1	n.176+71790T>C		intron_variant		3
ENSG00000285882	ENST00000648941.1	n.374-82203T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124317 AN: 152046 Hom.: 51316 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.818 AC: 124434 AN: 152164 Hom.: 51372 Cov.: 31 AF XY: 0.815 AC XY: 60632 AN XY: 74372

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.785

Gnomad4 ASJ AF: 0.804

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.775

Gnomad4 OTH AF: 0.795

Alfa AF: 0.808 Hom.: 10556

Bravo AF: 0.824

Asia WGS AF: 0.778 AC: 2708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs8049738; hg19: chr16-25970032;