Genetic Variant FRAT1:p.Pro82Arg (chr10-97319698-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005479.4(FRAT1):c.245C>G(p.Pro82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000981 in 1,172,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

FRAT1
NM_005479.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.48

Publications

0 publications found

Variant links:

Genes affected

FRAT1 (HGNC:3944): (FRAT regulator of WNT signaling pathway 1) The protein encoded by this gene belongs to the GSK-3-binding protein family. The protein inhibits GSK-3-mediated phosphorylation of beta-catenin and positively regulates the Wnt signaling pathway. It may function in tumor progression and in lymphomagenesis. [provided by RefSeq, Oct 2008]

FRAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046201736).

BS2

High AC in GnomAd4 at 23 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005479.4. 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
	FRAT1	NM_005479.4	MANE Select	c.245C>G	p.Pro82Arg	missense	Exon 1 of 1	NP_005470.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FRAT1	ENST00000371021.5	TSL:6 MANE Select	c.245C>G	p.Pro82Arg	missense	Exon 1 of 1	ENSP00000360060.3	Q92837

Frequencies

GnomAD3 genomes

AF:

0.000154

AC:

AN:

149398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000209

Gnomad OTH

AF:

0.000488

GnomAD4 exome

AF:

0.0000899

AC:

AN:

1023322

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

482932

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

20702

American (AMR)

AF:

0.000154

AC:

AN:

6482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11578

East Asian (EAS)

AF:

0.00

AC:

AN:

20544

South Asian (SAS)

AF:

0.00110

AC:

AN:

19068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18650

Middle Eastern (MID)

AF:

0.00268

AC:

AN:

2608

European-Non Finnish (NFE)

AF:

0.0000577

AC:

AN:

884440

Other (OTH)

AF:

0.000204

AC:

AN:

39250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000154

AC:

AN:

149506

Hom.:

Cov.:

AF XY:

0.0000959

AC XY:

AN XY:

72986

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41200

American (AMR)

AF:

0.00

AC:

AN:

15042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3428

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00104

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9602

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000209

AC:

AN:

67018

Other (OTH)

AF:

0.000483

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000869

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.32

(source)

DANN

Benign

0.61

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.33

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

PhyloP100

-1.5

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.8

REVEL

Benign

0.055

Sift

Benign

0.37

Sift4G

Benign

0.59

Polyphen

0.0020

Vest4

0.039

MutPred

0.56

Gain of helix (P = 0.005)

MVP

0.11

MPC

1.2

ClinPred

0.031

GERP RS

-0.080

PromoterAI

-0.0056

Neutral

(source)

Varity_R

0.040

gMVP

0.067

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over