rs7674470

Positions:

• chr4-11422111-T-C

Variant summary

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

The NM_005114.4(HS3ST1):​c.-109+6588A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,170 control chromosomes in the GnomAD database, including 23,470 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 0.55 (23470 hom., cov: 33)
• Consequence: HS3ST1 NM_005114.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HS3ST1	NM_005114.4	c.-109+6588A>G		intron_variant		ENST00000002596.6	NP_005105.1
HS3ST1	XM_011513913.4	c.-109+7314A>G		intron_variant			XP_011512215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HS3ST1	ENST00000002596.6	c.-109+6588A>G		intron_variant		1	NM_005114.4	ENSP00000002596	P1
HS3ST1	ENST00000510712.1	c.-109+7314A>G		intron_variant		2		ENSP00000422629
HS3ST1	ENST00000514690.5	c.-109+6352A>G		intron_variant		3		ENSP00000425673

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83508 AN: 152052 Hom.: 23444 Cov.: 33

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.549 AC: 83576 AN: 152170 Hom.: 23470 Cov.: 33 AF XY: 0.542 AC XY: 40323 AN XY: 74394

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.518

Alfa AF: 0.533 Hom.: 10094

Bravo AF: 0.542

Asia WGS AF: 0.418 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.46
DANN	Benign	0.61

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: rs7674470; hg19: chr4-11423735;