rs6982250

Variant names:

• chr8-69500215-C-T
• rs6982250
• NM_001128205.2:c.-228-1659C>T

Variant summary

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

The NM_001128205.2(SULF1):​c.-228-1659C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,030 control chromosomes in the GnomAD database, including 4,526 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 0.24 (4526 hom., cov: 33)
• Consequence: SULF1 NM_001128205.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 10 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128205.2. 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
	SULF1	NM_001128205.2	MANE Select	c.-228-1659C>T		intron	N/A	NP_001121677.1	Q8IWU6
	SULF1	NM_001412828.1		c.-228-1659C>T		intron	N/A	NP_001399757.1
	SULF1	NM_001412829.1		c.-228-1659C>T		intron	N/A	NP_001399758.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF1	ENST00000402687.9	TSL:1 MANE Select	c.-228-1659C>T		intron	N/A	ENSP00000385704.4	Q8IWU6
	SULF1	ENST00000419716.7	TSL:1	c.-228-1659C>T		intron	N/A	ENSP00000390315.3	Q8IWU6
	SULF1	ENST00000458141.6	TSL:1	c.-228-1659C>T		intron	N/A	ENSP00000403040.2	Q8IWU6

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35713 AN: 151912 Hom.: 4523 Cov.: 33

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.235 AC: 35737 AN: 152030 Hom.: 4526 Cov.: 33 AF XY: 0.238 AC XY: 17691 AN XY: 74306

African (AFR) AF: 0.247 AC: 10250 AN: 41448

American (AMR) AF: 0.298 AC: 4556 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 602 AN: 3462

East Asian (EAS) AF: 0.508 AC: 2632 AN: 5178

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4822

European-Finnish (FIN) AF: 0.257 AC: 2703 AN: 10536

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13180 AN: 67974

Other (OTH) AF: 0.244 AC: 517 AN: 2116

Alfa AF: 0.210 Hom.: 15987

Bravo AF: 0.242

Asia WGS AF: 0.357 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.72
PhyloP100		0.12
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6982250;

hg19: chr8-70412450;