8-81074718-T-C

Position:

• chr8-81074718-T-C

Variant summary

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

The NM_018440.4(PAG1):​c.-233-4548A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 151,918 control chromosomes in the GnomAD database, including 30,962 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 0.63 (30962 hom., cov: 31)
• Consequence: PAG1 NM_018440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAG1	NM_018440.4	c.-233-4548A>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.-233-4548A>G		intron_variant		2	NM_018440.4	ENSP00000220597	P1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95175 AN: 151800 Hom.: 30918 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.627 AC: 95274 AN: 151918 Hom.: 30962 Cov.: 31 AF XY: 0.636 AC XY: 47215 AN XY: 74266

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.620

Alfa AF: 0.518 Hom.: 10727

Bravo AF: 0.638

Asia WGS AF: 0.753 AC: 2619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.033
DANN	Benign	0.77

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: rs5003154; hg19: chr8-81986953;