rs6012506

Variant names:

• chr20-48669099-A-G
• rs6012506
• NM_020820.4:c.1666-2744T>C

Variant summary

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

The NM_020820.4(PREX1):​c.1666-2744T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,430 control chromosomes in the GnomAD database, including 23,285 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 0.54 (23285 hom., cov: 29)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PREX1	NM_020820.4	c.1666-2744T>C		intron_variant	Intron 14 of 39	ENST00000371941.4	NP_065871.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PREX1	ENST00000371941.4	c.1666-2744T>C		intron_variant	Intron 14 of 39	1	NM_020820.4	ENSP00000361009.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81315 AN: 151312 Hom.: 23244 Cov.: 29

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.538 AC: 81414 AN: 151430 Hom.: 23285 Cov.: 29 AF XY: 0.535 AC XY: 39504 AN XY: 73900

African (AFR) AF: 0.745 AC: 30725 AN: 41228

American (AMR) AF: 0.521 AC: 7939 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1741 AN: 3466

East Asian (EAS) AF: 0.428 AC: 2184 AN: 5108

South Asian (SAS) AF: 0.650 AC: 3098 AN: 4764

European-Finnish (FIN) AF: 0.375 AC: 3944 AN: 10516

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.444 AC: 30079 AN: 67800

Other (OTH) AF: 0.545 AC: 1148 AN: 2106

Alfa AF: 0.496 Hom.: 2540

Bravo AF: 0.551

Asia WGS AF: 0.574 AC: 1994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.035
DANN	Benign	0.34
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs6012506; hg19: chr20-47285637;