rs4809718

Variant names:

• chr20-48694450-T-A
• rs4809718
• NM_020820.4:c.918-1660A>T

Variant summary

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

The NM_020820.4(PREX1):​c.918-1660A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,114 control chromosomes in the GnomAD database, including 10,819 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 0.32 (10819 hom., cov: 32)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

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.918-1660A>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.918-1660A>T		intron	N/A	ENSP00000361009.3	Q8TCU6-1
	PREX1	ENST00000935959.1		c.846-1660A>T		intron	N/A	ENSP00000606018.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48373 AN: 151996 Hom.: 10793 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.318 AC: 48440 AN: 152114 Hom.: 10819 Cov.: 32 AF XY: 0.313 AC XY: 23245 AN XY: 74362

African (AFR) AF: 0.639 AC: 26482 AN: 41454

American (AMR) AF: 0.220 AC: 3356 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 803 AN: 3468

East Asian (EAS) AF: 0.0945 AC: 489 AN: 5174

South Asian (SAS) AF: 0.256 AC: 1238 AN: 4830

European-Finnish (FIN) AF: 0.150 AC: 1590 AN: 10590

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13640 AN: 67998

Other (OTH) AF: 0.288 AC: 607 AN: 2110

Alfa AF: 0.267 Hom.: 874

Bravo AF: 0.334

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.58
DANN	Benign	0.46
PhyloP100		-0.97
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: rs4809718; hg19: chr20-47310988;