rs6982250

Positions:

• chr8-69500215-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULF1	NM_001128205.2	c.-228-1659C>T		intron_variant		ENST00000402687.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULF1	ENST00000402687.9	c.-228-1659C>T		intron_variant		1	NM_001128205.2	P1

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

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.244

Alfa AF: 0.205 Hom.: 7123

Bravo AF: 0.242

Asia WGS AF: 0.357 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs6982250; hg19: chr8-70412450;