rs2726165

Variant names:

• chr4-107601860-C-T
• rs2726165
• ENST00000514815.1:n.175-11463G>A

Variant summary

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

The ENST00000514815.1(PAPSS1):​n.175-11463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,048 control chromosomes in the GnomAD database, including 772 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 0.085 (772 hom., cov: 31)
• Consequence: PAPSS1 ENST00000514815.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000514815.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS1	ENST00000514815.1	TSL:5	n.175-11463G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12854 AN: 151930 Hom.: 769 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0644

Gnomad ASJ AF: 0.0747

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0987

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

GnomAD4 genome AF: 0.0847 AC: 12881 AN: 152048 Hom.: 772 Cov.: 31 AF XY: 0.0816 AC XY: 6064 AN XY: 74342

African (AFR) AF: 0.173 AC: 7182 AN: 41454

American (AMR) AF: 0.0642 AC: 981 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 259 AN: 3466

East Asian (EAS) AF: 0.102 AC: 528 AN: 5172

South Asian (SAS) AF: 0.0262 AC: 126 AN: 4816

European-Finnish (FIN) AF: 0.0190 AC: 201 AN: 10576

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0493 AC: 3354 AN: 67970

Other (OTH) AF: 0.103 AC: 217 AN: 2110

Alfa AF: 0.0666 Hom.: 298

Bravo AF: 0.0930

Asia WGS AF: 0.0880 AC: 304 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.5
DANN	Benign	0.66
PhyloP100		-0.47

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2726165;

hg19: chr4-108523016;