NM_020820.4:c.415-3822A>G

Variant names:

• chr20-48738472-T-C
• rs6066835
• NM_020820.4:c.415-3822A>G

Variant summary

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

The NM_020820.4(PREX1):​c.415-3822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 152,256 control chromosomes in the GnomAD database, including 735 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 0.093 (735 hom., cov: 32)
• Consequence: PREX1 NM_020820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 11 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 (SAS) allele frequency at 95% confidence interval = 0.186 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.415-3822A>G		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.415-3822A>G		intron	N/A	ENSP00000361009.3
	PREX1	ENST00000935959.1		c.343-3822A>G		intron	N/A	ENSP00000606018.1

Frequencies

GnomAD3 genomes AF: 0.0928 AC: 14116 AN: 152138 Hom.: 732 Cov.: 32

Gnomad AFR AF: 0.0925

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.0928 AC: 14132 AN: 152256 Hom.: 735 Cov.: 32 AF XY: 0.0926 AC XY: 6894 AN XY: 74452

African (AFR) AF: 0.0925 AC: 3840 AN: 41526

American (AMR) AF: 0.111 AC: 1699 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3470

East Asian (EAS) AF: 0.166 AC: 859 AN: 5184

South Asian (SAS) AF: 0.196 AC: 948 AN: 4826

European-Finnish (FIN) AF: 0.0311 AC: 330 AN: 10616

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0840 AC: 5712 AN: 68024

Other (OTH) AF: 0.118 AC: 249 AN: 2110

Alfa AF: 0.0900 Hom.: 683

Bravo AF: 0.0970

Asia WGS AF: 0.158 AC: 550 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	4.4
DANN	Benign	0.33
PhyloP100		-0.18
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: rs6066835; hg19: chr20-47355009;