rs2921010

chr8-8372845-G-Achr8-8372845-G-T

Variant summary

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

The NM_001080826.3(PRAG1):c.2162+3402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,084 control chromosomes in the GnomAD database, including 3,442 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 0.20 (3442 hom., cov: 33)
• Consequence: PRAG1 NM_001080826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992

Genes affected

PRAG1 (HGNC:25438): (PEAK1 related, kinase-activating pseudokinase 1) This gene encodes an enzyme that belongs to the tyrosine protein kinase family. A similar protein in rat binds to Rho family GTPase 2 (Rnd2) and regulates neurite outgrowth via activation of Ras homolog gene family, member A (RhoA). [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRAG1	NM_001080826.3	c.2162+3402C>T		intron_variant		ENST00000615670.5
PRAG1	NM_001369759.1	c.2162+3402C>T		intron_variant
PRAG1	NR_163138.1	n.2368+3402C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRAG1	ENST00000615670.5	c.2162+3402C>T		intron_variant		5	NM_001080826.3	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29612 AN: 151966 Hom.: 3425 Cov.: 33

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.195 AC: 29664 AN: 152084 Hom.: 3442 Cov.: 33 AF XY: 0.192 AC XY: 14258 AN XY: 74354

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.198

Alfa AF: 0.163 Hom.: 4401

Bravo AF: 0.202

Asia WGS AF: 0.205 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.2
Dann	Benign	0.60

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: rs2921010; hg19: chr8-8230361;