rs4451005

Positions:

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

Variant summary

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

The ENST00000514815.1(PAPSS1):​n.175-2218A>T variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS1	ENST00000514815.1	n.175-2218A>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0748

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.224

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4451005; hg19: chr4-108513771;