8-69467849-G-T

Variant names:

• chr8-69467849-G-T
• rs2583086
• ENST00000458141.6:c.-229+899G>T

Variant summary

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

The ENST00000458141.6(SULF1):​c.-229+899G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 151,828 control chromosomes in the GnomAD database, including 6,427 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 0.29 (6427 hom., cov: 32)
• Consequence: SULF1 ENST00000458141.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.871
• Publications: 4 publications found

Genes affected

SULF1 (HGNC:20391): (sulfatase 1) This gene encodes an extracellular heparan sulfate endosulfatase. The encoded enzyme selectively removes 6-O-sulfate groups from heparan sulfate chains of heparan sulfate proteoglycans (HSPGs). The enzyme is secreted through the Golgi and is subsequently localized to the cell surface. The expression of this gene may be down-regulated in several types of cancer, including hepatocellular (HCC), ovarian and breast cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

LINC01603 (HGNC:51652): (long intergenic non-protein coding RNA 1603)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000458141.6. 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
	SULF1	NM_001412828.1		c.-391+899G>T		intron	N/A	NP_001399757.1
	SULF1	NM_001412829.1		c.-229+899G>T		intron	N/A	NP_001399758.1
	SULF1	NM_001412832.1		c.-229+899G>T		intron	N/A	NP_001399761.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF1	ENST00000458141.6	TSL:1	c.-229+899G>T		intron	N/A	ENSP00000403040.2
	SULF1	ENST00000260128.8	TSL:5	c.-391+899G>T		intron	N/A	ENSP00000260128.4
	SULF1	ENST00000529134.5	TSL:4	c.-229+760G>T		intron	N/A	ENSP00000432178.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43663 AN: 151710 Hom.: 6420 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.288 AC: 43689 AN: 151828 Hom.: 6427 Cov.: 32 AF XY: 0.284 AC XY: 21082 AN XY: 74196

African (AFR) AF: 0.328 AC: 13596 AN: 41390

American (AMR) AF: 0.245 AC: 3738 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3470

East Asian (EAS) AF: 0.144 AC: 746 AN: 5168

South Asian (SAS) AF: 0.184 AC: 883 AN: 4804

European-Finnish (FIN) AF: 0.256 AC: 2693 AN: 10528

Middle Eastern (MID) AF: 0.241 AC: 70 AN: 290

European-Non Finnish (NFE) AF: 0.293 AC: 19916 AN: 67894

Other (OTH) AF: 0.282 AC: 593 AN: 2106

Alfa AF: 0.290 Hom.: 24719

Bravo AF: 0.295

Asia WGS AF: 0.210 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.87
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: rs2583086; hg19: chr8-70380084;