rs79164465

Variant names:

• chr20-48627879-C-T
• rs79164465
• NM_020820.4:c.4851G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-48627879-C-T
• chr20-48627879-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_020820.4(PREX1):​c.4851G>A​(p.Thr1617Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,612,976 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (30 hom.)
• Consequence: PREX1 NM_020820.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.68
• Publications: 2 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 20-48627879-C-T is Benign according to our data. Variant chr20-48627879-C-T is described in ClinVar as Benign. ClinVar VariationId is 770000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.68 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00359 (546/152290) while in subpopulation EAS AF = 0.0195 (101/5168). AF 95% confidence interval is 0.0165. There are 7 homozygotes in GnomAd4. There are 300 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 546 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.4851G>A	p.Thr1617Thr	synonymous	Exon 38 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.4851G>A	p.Thr1617Thr	synonymous	Exon 38 of 40	ENSP00000361009.3	Q8TCU6-1
	PREX1	ENST00000935959.1		c.4779G>A	p.Thr1593Thr	synonymous	Exon 37 of 39	ENSP00000606018.1
	PREX1	ENST00000482556.5	TSL:2	n.*269G>A		non_coding_transcript_exon	Exon 20 of 22	ENSP00000434632.1	H0YDZ4

Frequencies

GnomAD3 genomes AF: 0.00358 AC: 545 AN: 152172 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00994

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0195

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00536 AC: 1339 AN: 249726 AF XY: 0.00515

Gnomad AFR exome AF: 0.00609

Gnomad AMR exome AF: 0.0140

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0192

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00194 AC: 2829 AN: 1460686 Hom.: 30 Cov.: 33 AF XY: 0.00220 AC XY: 1600 AN XY: 726634

African (AFR) AF: 0.00580 AC: 194 AN: 33458

American (AMR) AF: 0.0133 AC: 595 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.0189 AC: 749 AN: 39700

South Asian (SAS) AF: 0.0128 AC: 1105 AN: 86144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53094

Middle Eastern (MID) AF: 0.000942 AC: 5 AN: 5308

European-Non Finnish (NFE) AF: 0.0000243 AC: 27 AN: 1111892

Other (OTH) AF: 0.00255 AC: 154 AN: 60324

GnomAD4 genome AF: 0.00359 AC: 546 AN: 152290 Hom.: 7 Cov.: 32 AF XY: 0.00403 AC XY: 300 AN XY: 74466

African (AFR) AF: 0.00484 AC: 201 AN: 41556

American (AMR) AF: 0.00993 AC: 152 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5168

South Asian (SAS) AF: 0.0174 AC: 84 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000149 Hom.: 0

Bravo AF: 0.00417

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	3.5
DANN	Benign	0.77
PhyloP100		-1.7
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: rs79164465; hg19: chr20-47244417; COSMIC: COSV107457347;