rs16881446

Variant names:

• chr4-11406961-T-C
• rs16881446
• NM_005114.4:c.-108-6848A>G

Variant summary

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

The NM_005114.4(HS3ST1):​c.-108-6848A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,000 control chromosomes in the GnomAD database, including 5,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (★).

• Frequency: Genomes: 𝑓 0.27 (5581 hom., cov: 32)
• Consequence: HS3ST1 NM_005114.4 intron
• Clinical Significance: risk factor criteria provided, single submitter O:1
• Conservation: PhyloP100: -1.49
• Publications: 5 publications found

Genes affected

HS3ST1 (HGNC:5194): (heparan sulfate-glucosamine 3-sulfotransferase 1) Heparan sulfate biosynthetic enzymes are key components in generating a myriad of distinct heparan sulfate fine structures that carry out multiple biologic activities. The enzyme encoded by this gene is a member of the heparan sulfate biosynthetic enzyme family. It possesses both heparan sulfate glucosaminyl 3-O-sulfotransferase activity, anticoagulant heparan sulfate conversion activity, and is a rate limiting enzyme for synthesis of anticoagulant heparan. This enzyme is an intraluminal Golgi resident protein. [provided by RefSeq, Jul 2008]

ENSG00000308608 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005114.4. 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
	HS3ST1	NM_005114.4	MANE Select	c.-108-6848A>G		intron	N/A	NP_005105.1	O14792

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HS3ST1	ENST00000002596.6	TSL:1 MANE Select	c.-108-6848A>G		intron	N/A	ENSP00000002596.5	O14792
	HS3ST1	ENST00000952062.1		c.-193-2295A>G		intron	N/A	ENSP00000622121.1
	HS3ST1	ENST00000952063.1		c.-108-6848A>G		intron	N/A	ENSP00000622122.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40954 AN: 151882 Hom.: 5575 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.270 AC: 40980 AN: 152000 Hom.: 5581 Cov.: 32 AF XY: 0.271 AC XY: 20153 AN XY: 74288

African (AFR) AF: 0.286 AC: 11840 AN: 41444

American (AMR) AF: 0.227 AC: 3462 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3464

East Asian (EAS) AF: 0.183 AC: 946 AN: 5168

South Asian (SAS) AF: 0.322 AC: 1550 AN: 4816

European-Finnish (FIN) AF: 0.323 AC: 3409 AN: 10560

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18121 AN: 67958

Other (OTH) AF: 0.254 AC: 537 AN: 2114

Alfa AF: 0.257 Hom.: 6736

Bravo AF: 0.262

Asia WGS AF: 0.299 AC: 1040 AN: 3478

ClinVar

ClinVar submissions

Significance: risk factor

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	-	Arteriosclerosis disorder;C1956346:Coronary artery disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.31
DANN	Benign	0.32
PhyloP100		-1.5
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: rs16881446; hg19: chr4-11408585;