rs1888636

Variant names:

• chr9-116177055-T-A
• rs1888636
• NM_002581.5:c.416-10099T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-116177055-T-A
• chr9-116177055-T-G

Variant summary

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

The NM_002581.5(PAPPA):​c.416-10099T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,642 control chromosomes in the GnomAD database, including 17,999 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 0.44 (17999 hom., cov: 29)
• Consequence: PAPPA NM_002581.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 2 publications found

Genes affected

PAPPA (HGNC:8602): (pappalysin 1) This gene encodes a secreted metalloproteinase which cleaves insulin-like growth factor binding proteins (IGFBPs). Following IGFBP cleavage, insulin growth factors dissociate from IGFBPs and bind to IGF receptors, resulting in activation of the IGF pathway. The encoded protein plays a role in bone formation, inflammation, wound healing and female fertility. Enhanced expression of this protein is associated with diabetic nephropathy in human patients and this protein may promote tumor invasion and growth in various human cancers. [provided by RefSeq, Aug 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPPA	NM_002581.5	c.416-10099T>A		intron_variant	Intron 1 of 21	ENST00000328252.4	NP_002572.2
PAPPA	XM_017014784.3	c.416-10099T>A		intron_variant	Intron 1 of 20		XP_016870273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPPA	ENST00000328252.4	c.416-10099T>A		intron_variant	Intron 1 of 21	1	NM_002581.5	ENSP00000330658.3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67001 AN: 151520 Hom.: 18002 Cov.: 29

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.442 AC: 67019 AN: 151642 Hom.: 17999 Cov.: 29 AF XY: 0.439 AC XY: 32505 AN XY: 74082

African (AFR) AF: 0.160 AC: 6621 AN: 41406

American (AMR) AF: 0.376 AC: 5739 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1572 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1055 AN: 5098

South Asian (SAS) AF: 0.413 AC: 1976 AN: 4784

European-Finnish (FIN) AF: 0.661 AC: 6911 AN: 10448

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41423 AN: 67882

Other (OTH) AF: 0.426 AC: 896 AN: 2104

Alfa AF: 0.523 Hom.: 2812

Bravo AF: 0.407

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.75
DANN	Benign	0.45
PhyloP100		-0.63
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: rs1888636; hg19: chr9-118939334;