chr8-69581739-G-A

Variant names:

• chr8-69581739-G-A
• rs13273088
• NM_001128205.2:c.413-4618G>A

Variant summary

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

The NM_001128205.2(SULF1):​c.413-4618G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,124 control chromosomes in the GnomAD database, including 49,525 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 0.80 (49525 hom., cov: 32)
• Consequence: SULF1 NM_001128205.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39
• Publications: 13 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=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128205.2. 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.413-4618G>A		intron	N/A	NP_001121677.1
	SULF1	NM_001412828.1		c.413-4618G>A		intron	N/A	NP_001399757.1
	SULF1	NM_001412829.1		c.413-4618G>A		intron	N/A	NP_001399758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULF1	ENST00000402687.9	TSL:1 MANE Select	c.413-4618G>A		intron	N/A	ENSP00000385704.4
	SULF1	ENST00000419716.7	TSL:1	c.413-4618G>A		intron	N/A	ENSP00000390315.3
	SULF1	ENST00000458141.6	TSL:1	c.413-4618G>A		intron	N/A	ENSP00000403040.2

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122318 AN: 152006 Hom.: 49476 Cov.: 32

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.795

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.805 AC: 122421 AN: 152124 Hom.: 49525 Cov.: 32 AF XY: 0.803 AC XY: 59721 AN XY: 74346

African (AFR) AF: 0.868 AC: 36015 AN: 41508

American (AMR) AF: 0.660 AC: 10072 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2910 AN: 3468

East Asian (EAS) AF: 0.830 AC: 4287 AN: 5168

South Asian (SAS) AF: 0.795 AC: 3822 AN: 4808

European-Finnish (FIN) AF: 0.796 AC: 8433 AN: 10590

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54368 AN: 67996

Other (OTH) AF: 0.797 AC: 1682 AN: 2110

Alfa AF: 0.805 Hom.: 128231

Bravo AF: 0.796

Asia WGS AF: 0.809 AC: 2815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		1.4
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: rs13273088; hg19: chr8-70493974;