rs2016459

Variant names:

• chr8-80993079-A-C
• rs2016459
• NM_018440.4:c.125+24T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PAG1	NM_018440.4	c.125+24T>G		intron_variant	Intron 4 of 8	ENST00000220597.4	NP_060910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAG1	ENST00000220597.4	c.125+24T>G		intron_variant	Intron 4 of 8	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

GnomAD2 exomes AF: 0.366 AC: 87218 AN: 238352 AF XY: 0.365

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 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

African (AFR) AF: 0.766 AC: 24538 AN: 32044

American (AMR) AF: 0.227 AC: 9810 AN: 43158

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 10913 AN: 25166

East Asian (EAS) AF: 0.498 AC: 18990 AN: 38104

South Asian (SAS) AF: 0.441 AC: 35743 AN: 81096

European-Finnish (FIN) AF: 0.379 AC: 19931 AN: 52568

Middle Eastern (MID) AF: 0.452 AC: 2546 AN: 5628

European-Non Finnish (NFE) AF: 0.299 AC: 324550 AN: 1084772

Other (OTH) AF: 0.370 AC: 21731 AN: 58658

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

African (AFR) AF: 0.751 AC: 31132 AN: 41454

American (AMR) AF: 0.321 AC: 4901 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3466

East Asian (EAS) AF: 0.502 AC: 2599 AN: 5178

South Asian (SAS) AF: 0.446 AC: 2152 AN: 4822

European-Finnish (FIN) AF: 0.372 AC: 3930 AN: 10574

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20969 AN: 67980

Other (OTH) AF: 0.453 AC: 954 AN: 2108

Alfa AF: 0.348 Hom.: 2570

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
PhyloP100		-0.61
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: rs2016459; hg19: chr8-81905314; COSMIC: COSV55056125;