chr8-81104029-G-A

Position:

• chr8-81104029-G-A

Variant summary

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

The NM_018440.4(PAG1):​c.-234+7562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,020 control chromosomes in the GnomAD database, including 15,082 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 0.41 (15082 hom., cov: 32)
• Consequence: PAG1 NM_018440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAG1	NM_018440.4	c.-234+7562C>T		intron_variant		ENST00000220597.4	NP_060910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAG1	ENST00000220597.4	c.-234+7562C>T		intron_variant		2	NM_018440.4	ENSP00000220597	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62040 AN: 151902 Hom.: 15050 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.409 AC: 62127 AN: 152020 Hom.: 15082 Cov.: 32 AF XY: 0.405 AC XY: 30068 AN XY: 74288

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.401

Alfa AF: 0.315 Hom.: 9175

Bravo AF: 0.414

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.98
DANN	Benign	0.75

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: rs10504729; hg19: chr8-82016264;