8-69605800-A-G

Position:

• chr8-69605800-A-G

Variant summary

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

The NM_001128205.2(SULF1):​c.1377+868A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,152 control chromosomes in the GnomAD database, including 45,289 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 0.77 (45289 hom., cov: 32)
• Consequence: SULF1 NM_001128205.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULF1	NM_001128205.2	c.1377+868A>G		intron_variant		ENST00000402687.9	NP_001121677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULF1	ENST00000402687.9	c.1377+868A>G		intron_variant		1	NM_001128205.2	ENSP00000385704.4

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116535 AN: 152032 Hom.: 45236 Cov.: 32

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.703

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.767 AC: 116648 AN: 152152 Hom.: 45289 Cov.: 32 AF XY: 0.764 AC XY: 56782 AN XY: 74358

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.720

Gnomad4 OTH AF: 0.746

Alfa AF: 0.737 Hom.: 5560

Bravo AF: 0.775

Asia WGS AF: 0.775 AC: 2697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.57
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4737999; hg19: chr8-70518035;