chr20-48624820-C-T

Variant names:

• chr20-48624820-C-T
• rs2664570
• NM_020820.4:c.*1065G>A

Variant summary

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

The NM_020820.4(PREX1):​c.*1065G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,294 control chromosomes in the GnomAD database, including 2,844 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 0.19 (2843 hom., cov: 33)
  • Exomes 𝑓: 0.13 (1 hom.)
• Consequence: PREX1 NM_020820.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 9 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.254 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.*1065G>A		3_prime_UTR	Exon 40 of 40	NP_065871.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PREX1	ENST00000371941.4	TSL:1 MANE Select	c.*1065G>A		3_prime_UTR	Exon 40 of 40	ENSP00000361009.3	Q8TCU6-1
	PREX1	ENST00000935959.1		c.*1065G>A		3_prime_UTR	Exon 39 of 39	ENSP00000606018.1
	PREX1	ENST00000482556.5	TSL:2	n.*1463G>A		non_coding_transcript_exon	Exon 22 of 22	ENSP00000434632.1	H0YDZ4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29175 AN: 152106 Hom.: 2841 Cov.: 33

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.129 AC: 9 AN: 70 Hom.: 1 Cov.: 0 AF XY: 0.0926 AC XY: 5 AN XY: 54

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.143 AC: 8 AN: 56

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.192 AC: 29201 AN: 152224 Hom.: 2843 Cov.: 33 AF XY: 0.191 AC XY: 14209 AN XY: 74410

African (AFR) AF: 0.174 AC: 7214 AN: 41518

American (AMR) AF: 0.232 AC: 3545 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3466

East Asian (EAS) AF: 0.122 AC: 631 AN: 5180

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4824

European-Finnish (FIN) AF: 0.169 AC: 1792 AN: 10606

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.194 AC: 13202 AN: 68010

Other (OTH) AF: 0.222 AC: 469 AN: 2114

Alfa AF: 0.197 Hom.: 3927

Bravo AF: 0.192

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.67
PhyloP100		-0.11
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: rs2664570; hg19: chr20-47241358;