ENST00000521946.5:n.2892G>A

Variant names:

• chr8-69659296-G-A
• rs6990375
• ENST00000521946.5:n.2892G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000521946.5(SULF1):​n.2892G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 423,916 control chromosomes in the GnomAD database, including 19,992 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 0.31 (7455 hom., cov: 32)
  • Exomes 𝑓: 0.30 (12537 hom.)
• Consequence: SULF1 ENST00000521946.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48
• Publications: 28 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000521946.5. 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_001128205.2	MANE Select	c.*761G>A		3_prime_UTR	Exon 23 of 23	NP_001121677.1
	SULF1	NM_001412828.1		c.3343G>A	p.Ala1115Thr	missense	Exon 22 of 22	NP_001399757.1
	SULF1	NM_001412829.1		c.3343G>A	p.Ala1115Thr	missense	Exon 21 of 21	NP_001399758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF1	ENST00000521946.5	TSL:1	n.2892G>A		non_coding_transcript_exon	Exon 17 of 17
	SULF1	ENST00000402687.9	TSL:1 MANE Select	c.*761G>A		3_prime_UTR	Exon 23 of 23	ENSP00000385704.4
	SULF1	ENST00000419716.7	TSL:1	c.*761G>A		3_prime_UTR	Exon 22 of 22	ENSP00000390315.3

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46787 AN: 151896 Hom.: 7458 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.326

GnomAD2 exomes AF: 0.321 AC: 35361 AN: 110102 AF XY: 0.312

Gnomad AFR exome AF: 0.287

Gnomad AMR exome AF: 0.434

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.373

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.321

GnomAD4 exome AF: 0.297 AC: 80745 AN: 271904 Hom.: 12537 Cov.: 0 AF XY: 0.286 AC XY: 44285 AN XY: 154738

African (AFR) AF: 0.280 AC: 2014 AN: 7182

American (AMR) AF: 0.426 AC: 9212 AN: 21610

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 2202 AN: 8208

East Asian (EAS) AF: 0.367 AC: 3305 AN: 8994

South Asian (SAS) AF: 0.211 AC: 11251 AN: 53366

European-Finnish (FIN) AF: 0.333 AC: 3959 AN: 11898

Middle Eastern (MID) AF: 0.271 AC: 695 AN: 2568

European-Non Finnish (NFE) AF: 0.305 AC: 44340 AN: 145206

Other (OTH) AF: 0.293 AC: 3767 AN: 12872

GnomAD4 genome AF: 0.308 AC: 46807 AN: 152012 Hom.: 7455 Cov.: 32 AF XY: 0.311 AC XY: 23085 AN XY: 74286

African (AFR) AF: 0.280 AC: 11607 AN: 41444

American (AMR) AF: 0.412 AC: 6303 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 921 AN: 3470

East Asian (EAS) AF: 0.387 AC: 1997 AN: 5156

South Asian (SAS) AF: 0.197 AC: 943 AN: 4798

European-Finnish (FIN) AF: 0.333 AC: 3519 AN: 10572

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20458 AN: 67974

Other (OTH) AF: 0.328 AC: 691 AN: 2108

Alfa AF: 0.304 Hom.: 30711

Bravo AF: 0.315

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.87
PhyloP100		3.5
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: rs6990375; hg19: chr8-70571531; COSMIC: COSV52672328; COSMIC: COSV52672328;