rs2016459

Positions:

• chr8-80993079-A-C
• chr8-80993079-A-T

Variant summary

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

The NM_018440.4(PAG1):​c.125+24T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,573,262 control chromosomes in the GnomAD database, including 101,899 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 0.45 (18386 hom., cov: 32)
  • Exomes 𝑓: 0.33 (83513 hom.)
• Consequence: PAG1 NM_018440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615

Genes affected

PAG1 (HGNC:30043): (phosphoprotein membrane anchor with glycosphingolipid microdomains 1) The protein encoded by this gene is a type III transmembrane adaptor protein that binds to the tyrosine kinase csk protein. It is thought to be involved in the regulation of T cell activation. [provided by RefSeq, Jul 2008]

PAG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAG1	NM_018440.4	c.125+24T>G		intron_variant		ENST00000220597.4	NP_060910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAG1	ENST00000220597.4	c.125+24T>G		intron_variant		2	NM_018440.4	ENSP00000220597.3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68513 AN: 151948 Hom.: 18341 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.455

GnomAD3 exomes AF: 0.366 AC: 87218 AN: 238352 Hom.: 18058 AF XY: 0.365 AC XY: 47090 AN XY: 128984

Gnomad AFR exome AF: 0.760

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.425

Gnomad EAS exome AF: 0.481

Gnomad SAS exome AF: 0.430

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.315

Gnomad OTH exome AF: 0.347

GnomAD4 exome AF: 0.330 AC: 468752 AN: 1421194 Hom.: 83513 Cov.: 28 AF XY: 0.333 AC XY: 233963 AN XY: 702800

Gnomad4 AFR exome AF: 0.766

Gnomad4 AMR exome AF: 0.227

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.451 AC: 68606 AN: 152068 Hom.: 18386 Cov.: 32 AF XY: 0.452 AC XY: 33587 AN XY: 74352

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.453

Alfa AF: 0.338 Hom.: 2352

Bravo AF: 0.461

Asia WGS AF: 0.461 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs2016459; hg19: chr8-81905314; COSMIC: COSV55056125;