rs2426087

Variant names:

• chr20-48763274-G-A
• rs2426087
• NM_020820.4:c.220-15394C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_020820.4(PREX1):​c.220-15394C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 152,358 control chromosomes in the GnomAD database, including 36 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 0.020 (36 hom., cov: 32)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402
• Publications: 8 publications found

Genes affected

PREX1 (HGNC:32594): (phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1) The protein encoded by this gene acts as a guanine nucleotide exchange factor for the RHO family of small GTP-binding proteins (RACs). It has been shown to bind to and activate RAC1 by exchanging bound GDP for free GTP. The encoded protein, which is found mainly in the cytoplasm, is activated by phosphatidylinositol-3,4,5-trisphosphate and the beta-gamma subunits of heterotrimeric G proteins. [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=-0.75).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0197 (3003/152358) while in subpopulation NFE AF = 0.0291 (1977/68024). AF 95% confidence interval is 0.028. There are 36 homozygotes in GnomAd4. There are 1349 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3003 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PREX1	NM_020820.4	MANE Select	c.220-15394C>T		intron	N/A	NP_065871.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PREX1	ENST00000371941.4	TSL:1 MANE Select	c.220-15394C>T		intron	N/A	ENSP00000361009.3	Q8TCU6-1
	PREX1	ENST00000935959.1		c.220-18127C>T		intron	N/A	ENSP00000606018.1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 3005 AN: 152240 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0315

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

GnomAD4 genome AF: 0.0197 AC: 3003 AN: 152358 Hom.: 36 Cov.: 32 AF XY: 0.0181 AC XY: 1349 AN XY: 74508

African (AFR) AF: 0.00606 AC: 252 AN: 41586

American (AMR) AF: 0.0259 AC: 396 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4834

European-Finnish (FIN) AF: 0.00480 AC: 51 AN: 10628

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0291 AC: 1977 AN: 68024

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0220 Hom.: 17

Bravo AF: 0.0206

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.1
DANN	Benign	0.91
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

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: rs2426087; hg19: chr20-47379811; COSMIC: COSV64249547;