8-69577780-C-T

Position:

• chr8-69577780-C-T

Variant summary

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

The NM_001128205.2(SULF1):​c.412+1571C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,006 control chromosomes in the GnomAD database, including 4,963 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 0.24 (4963 hom., cov: 32)
• Consequence: SULF1 NM_001128205.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULF1	NM_001128205.2	c.412+1571C>T		intron_variant		ENST00000402687.9	NP_001121677.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULF1	ENST00000402687.9	c.412+1571C>T		intron_variant		1	NM_001128205.2	ENSP00000385704	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36834 AN: 151888 Hom.: 4964 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.242 AC: 36841 AN: 152006 Hom.: 4963 Cov.: 32 AF XY: 0.243 AC XY: 18052 AN XY: 74290

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.273

Alfa AF: 0.298 Hom.: 9821

Bravo AF: 0.236

Asia WGS AF: 0.241 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.84

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: rs10108002; hg19: chr8-70490015;