rs4810663

Variant names:

• chr20-47711762-C-T
• rs4810663
• NM_001387048.1:c.416-9092G>A

Variant summary

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

The NM_001387048.1(SULF2):​c.416-9092G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,186 control chromosomes in the GnomAD database, including 2,210 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 0.16 (2210 hom., cov: 33)
• Consequence: SULF2 NM_001387048.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 1 publications found

Genes affected

SULF2 (HGNC:20392): (sulfatase 2) Heparan sulfate proteoglycans (HSPGs) act as coreceptors for numerous heparin-binding growth factors and cytokines and are involved in cell signaling. Heparan sulfate 6-O-endosulfatases, such as SULF2, selectively remove 6-O-sulfate groups from heparan sulfate. This activity modulates the effects of heparan sulfate by altering binding sites for signaling molecules (Dai et al., 2005 [PubMed 16192265]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULF2	NM_001387048.1	c.416-9092G>A		intron_variant	Intron 3 of 20	ENST00000688720.1	NP_001373977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULF2	ENST00000688720.1	c.416-9092G>A		intron_variant	Intron 3 of 20		NM_001387048.1	ENSP00000508753.1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24854 AN: 152068 Hom.: 2203 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.164 AC: 24891 AN: 152186 Hom.: 2210 Cov.: 33 AF XY: 0.164 AC XY: 12199 AN XY: 74412

African (AFR) AF: 0.104 AC: 4309 AN: 41526

American (AMR) AF: 0.144 AC: 2208 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3472

East Asian (EAS) AF: 0.0520 AC: 270 AN: 5188

South Asian (SAS) AF: 0.169 AC: 817 AN: 4830

European-Finnish (FIN) AF: 0.259 AC: 2735 AN: 10568

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13404 AN: 67996

Other (OTH) AF: 0.155 AC: 326 AN: 2108

Alfa AF: 0.186 Hom.: 4543

Bravo AF: 0.152

Asia WGS AF: 0.128 AC: 450 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.61
PhyloP100		-1.2
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: rs4810663; hg19: chr20-46340506;