rs4451005

Variant names:

• chr4-107592615-T-A
• rs4451005
• ENST00000514815.1:n.175-2218A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-107592615-T-A
• chr4-107592615-T-C

Variant summary

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

The ENST00000514815.1(PAPSS1):​n.175-2218A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,742 control chromosomes in the GnomAD database, including 4,375 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 0.20 (4375 hom., cov: 33)
• Consequence: PAPSS1 ENST00000514815.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 1 publications found

Genes affected

PAPSS1 (HGNC:8603): (3'-phosphoadenosine 5'-phosphosulfate synthase 1) Three-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS) is the sulfate donor cosubstrate for all sulfotransferase (SULT) enzymes (Xu et al., 2000 [PubMed 10679223]). SULTs catalyze the sulfate conjugation of many endogenous and exogenous compounds, including drugs and other xenobiotics. In humans, PAPS is synthesized from adenosine 5-prime triphosphate (ATP) and inorganic sulfate by 2 isoforms, PAPSS1 and PAPSS2 (MIM 603005).[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 (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS1	ENST00000514815.1	n.175-2218A>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30996 AN: 151624 Hom.: 4364 Cov.: 33

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.204 AC: 31025 AN: 151742 Hom.: 4375 Cov.: 33 AF XY: 0.206 AC XY: 15293 AN XY: 74148

African (AFR) AF: 0.0748 AC: 3107 AN: 41528

American (AMR) AF: 0.288 AC: 4381 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3466

East Asian (EAS) AF: 0.355 AC: 1835 AN: 5176

South Asian (SAS) AF: 0.152 AC: 723 AN: 4762

European-Finnish (FIN) AF: 0.283 AC: 2984 AN: 10530

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.242 AC: 16432 AN: 67774

Other (OTH) AF: 0.224 AC: 473 AN: 2108

Alfa AF: 0.127 Hom.: 306

Bravo AF: 0.208

Asia WGS AF: 0.212 AC: 735 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.51
PhyloP100		-2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4451005; hg19: chr4-108513771;