rs6990375

Positions:

• chr8-69659296-G-A
• chr8-69659296-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001412828.1(SULF1):​c.3343G>A​(p.Ala1115Thr) variant causes a missense 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. 5/5 in silico tools predict 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 NM_001412828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48

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]

SULF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULF1	NM_001128205.2	c.*761G>A		3_prime_UTR_variant	23/23	ENST00000402687.9	NP_001121677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULF1	ENST00000402687.9	c.*761G>A		3_prime_UTR_variant	23/23	1	NM_001128205.2	ENSP00000385704.4

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

GnomAD3 exomes AF: 0.321 AC: 35361 AN: 110102 Hom.: 5877 AF XY: 0.312 AC XY: 18205 AN XY: 58356

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 SAS exome AF: 0.215

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

Gnomad4 AFR exome AF: 0.280

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.293

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

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.387

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.328

Alfa AF: 0.303 Hom.: 14682

Bravo AF: 0.315

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	13
DANN	Benign	0.87

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: rs6990375; hg19: chr8-70571531; COSMIC: COSV52672328; COSMIC: COSV52672328;