rs3802278

Variant names:

• chr8-69659078-G-A
• rs3802278
• NM_001128205.2:c.*543G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-69659078-G-A
• chr8-69659078-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001412828.1(SULF1):​c.3125G>A​(p.Arg1042His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 456,742 control chromosomes in the GnomAD database, including 23,037 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 0.33 (8278 hom., cov: 33)
  • Exomes 𝑓: 0.31 (14759 hom.)
• Consequence: SULF1 NM_001412828.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULF1	NM_001128205.2	c.*543G>A		3_prime_UTR_variant	Exon 23 of 23	ENST00000402687.9	NP_001121677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULF1	ENST00000402687.9	c.*543G>A		3_prime_UTR_variant	Exon 23 of 23	1	NM_001128205.2	ENSP00000385704.4

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49538 AN: 151986 Hom.: 8278 Cov.: 33

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.346

GnomAD3 exomes AF: 0.319 AC: 44799 AN: 140356 Hom.: 7467 AF XY: 0.309 AC XY: 23421 AN XY: 75836

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.425

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.370

Gnomad SAS exome AF: 0.222

Gnomad FIN exome AF: 0.325

Gnomad NFE exome AF: 0.304

Gnomad OTH exome AF: 0.322

GnomAD4 exome AF: 0.305 AC: 92967 AN: 304636 Hom.: 14759 Cov.: 0 AF XY: 0.295 AC XY: 51169 AN XY: 173442

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.426

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.326 AC: 49571 AN: 152106 Hom.: 8278 Cov.: 33 AF XY: 0.328 AC XY: 24410 AN XY: 74336

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.348

Alfa AF: 0.307 Hom.: 10453

Bravo AF: 0.334

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.69

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: rs3802278; hg19: chr8-70571313; COSMIC: COSV52672316; COSMIC: COSV52672316;