8-8340709-C-T

Variant names:

• chr8-8340709-C-T
• rs2945913
• NM_001080826.3:c.2163-1074G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080826.3(PRAG1):​c.2163-1074G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,222 control chromosomes in the GnomAD database, including 1,592 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 0.13 (1592 hom., cov: 33)
• Consequence: PRAG1 NM_001080826.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.39
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080826.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAG1	NM_001080826.3	MANE Select	c.2163-1074G>A		intron	N/A	NP_001074295.2
	PRAG1	NM_001369759.1		c.2163-1074G>A		intron	N/A	NP_001356688.1
	PRAG1	NR_163138.1		n.2460-1074G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRAG1	ENST00000615670.5	TSL:5 MANE Select	c.2163-1074G>A		intron	N/A	ENSP00000481109.1
	PRAG1	ENST00000933693.1		c.2163-1074G>A		intron	N/A	ENSP00000603752.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20106 AN: 152104 Hom.: 1594 Cov.: 33

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.132 AC: 20091 AN: 152222 Hom.: 1592 Cov.: 33 AF XY: 0.138 AC XY: 10274 AN XY: 74426

African (AFR) AF: 0.0524 AC: 2176 AN: 41554

American (AMR) AF: 0.205 AC: 3133 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1387 AN: 5182

South Asian (SAS) AF: 0.159 AC: 766 AN: 4826

European-Finnish (FIN) AF: 0.208 AC: 2196 AN: 10572

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9611 AN: 68006

Other (OTH) AF: 0.145 AC: 306 AN: 2110

Alfa AF: 0.135 Hom.: 2531

Bravo AF: 0.130

Asia WGS AF: 0.196 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.10
DANN	Benign	0.57
PhyloP100		-3.4

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: rs2945913; hg19: chr8-8198225;