chr8-69659078-G-A

Variant names:

• chr8-69659078-G-A
• rs3802278
• ENST00000521946.5:n.2674G>A

Variant summary

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

The ENST00000521946.5(SULF1):​n.2674G>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 0.312 in 456,742 control chromosomes in the GnomAD database, including 23,037 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 0.33 (8278 hom., cov: 33)
  • Exomes 𝑓: 0.31 (14759 hom.)
• Consequence: SULF1 ENST00000521946.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 16 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 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.*543G>A		3_prime_UTR	Exon 23 of 23	NP_001121677.1
	SULF1	NM_001412828.1		c.3125G>A	p.Arg1042His	missense	Exon 22 of 22	NP_001399757.1
	SULF1	NM_001412829.1		c.3125G>A	p.Arg1042His	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.2674G>A		non_coding_transcript_exon	Exon 17 of 17
	SULF1	ENST00000402687.9	TSL:1 MANE Select	c.*543G>A		3_prime_UTR	Exon 23 of 23	ENSP00000385704.4
	SULF1	ENST00000419716.7	TSL:1	c.*543G>A		3_prime_UTR	Exon 22 of 22	ENSP00000390315.3

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

GnomAD2 exomes AF: 0.319 AC: 44799 AN: 140356 AF XY: 0.309

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 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

African (AFR) AF: 0.333 AC: 2876 AN: 8628

American (AMR) AF: 0.426 AC: 11630 AN: 27284

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 3155 AN: 10790

East Asian (EAS) AF: 0.369 AC: 3400 AN: 9210

South Asian (SAS) AF: 0.224 AC: 13406 AN: 59740

European-Finnish (FIN) AF: 0.333 AC: 4297 AN: 12896

Middle Eastern (MID) AF: 0.302 AC: 839 AN: 2782

European-Non Finnish (NFE) AF: 0.308 AC: 49041 AN: 158998

Other (OTH) AF: 0.302 AC: 4323 AN: 14308

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

African (AFR) AF: 0.331 AC: 13740 AN: 41504

American (AMR) AF: 0.424 AC: 6489 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3466

East Asian (EAS) AF: 0.386 AC: 1995 AN: 5162

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4822

European-Finnish (FIN) AF: 0.335 AC: 3535 AN: 10564

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20688 AN: 67972

Other (OTH) AF: 0.348 AC: 737 AN: 2116

Alfa AF: 0.311 Hom.: 23392

Bravo AF: 0.334

Asia WGS AF: 0.286 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		0.17
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: rs3802278; hg19: chr8-70571313; COSMIC: COSV52672316; COSMIC: COSV52672316;