chr8-69660769-G-A

Variant names:

• chr8-69660769-G-A
• rs3087714
• NM_001128205.2:c.*2234G>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.*2234G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,348 control chromosomes in the GnomAD database, including 7,136 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 0.30 (7108 hom., cov: 33)
  • Exomes 𝑓: 0.34 (28 hom.)
• Consequence: SULF1 NM_001128205.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.757
• Publications: 8 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=-0.49).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULF1	NM_001128205.2	c.*2234G>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.*2234G>A		3_prime_UTR_variant	Exon 23 of 23	1	NM_001128205.2	ENSP00000385704.4
SULF1	ENST00000458141.6	c.*2234G>A		3_prime_UTR_variant	Exon 22 of 22	1		ENSP00000403040.2
SULF1	ENST00000260128.8	c.*2234G>A		3_prime_UTR_variant	Exon 23 of 23	5		ENSP00000260128.4

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45399 AN: 151798 Hom.: 7110 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.345 AC: 149 AN: 432 Hom.: 28 Cov.: 0 AF XY: 0.327 AC XY: 85 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.343 AC: 146 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.299 AC: 45419 AN: 151916 Hom.: 7108 Cov.: 33 AF XY: 0.302 AC XY: 22445 AN XY: 74240

African (AFR) AF: 0.248 AC: 10263 AN: 41422

American (AMR) AF: 0.409 AC: 6247 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3468

East Asian (EAS) AF: 0.387 AC: 2003 AN: 5170

South Asian (SAS) AF: 0.199 AC: 958 AN: 4816

European-Finnish (FIN) AF: 0.335 AC: 3526 AN: 10522

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.301 AC: 20447 AN: 67952

Other (OTH) AF: 0.325 AC: 686 AN: 2108

Alfa AF: 0.304 Hom.: 21655

Bravo AF: 0.304

Asia WGS AF: 0.274 AC: 952 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.7
DANN	Benign	0.60
PhyloP100		0.76
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: rs3087714; hg19: chr8-70573004;