dbSNP rs752436465: GARRE1:p.Ala52Gly (chr19-34300628-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014686.5(GARRE1):c.155C>G(p.Ala52Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A52V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GARRE1
NM_014686.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.91

Publications

0 publications found

Variant links:

Genes affected

GARRE1 (HGNC:29016): (granule associated Rac and RHOG effector 1) Enables CCR4-NOT complex binding activity and small GTPase binding activity. Involved in Rac protein signal transduction. Located in P-body. [provided by Alliance of Genome Resources, Apr 2022]

GARRE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045878917).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014686.5. 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
	GARRE1	NM_014686.5	MANE Select	c.155C>G	p.Ala52Gly	missense	Exon 2 of 14	NP_055501.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GARRE1	ENST00000299505.8	TSL:1 MANE Select	c.155C>G	p.Ala52Gly	missense	Exon 2 of 14	ENSP00000299505.4	O15063
GARRE1	ENST00000899721.1		c.155C>G	p.Ala52Gly	missense	Exon 2 of 14	ENSP00000569780.1
GARRE1	ENST00000932925.1		c.155C>G	p.Ala52Gly	missense	Exon 3 of 15	ENSP00000602984.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000800

AC:

AN:

249948

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461160

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726916

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52738

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111974

Other (OTH)

AF:

0.0000166

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

M_CAP

Benign

0.0052

MetaRNN

Benign

0.046

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

2.9

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.57

REVEL

Benign

0.10

Sift

Benign

0.080

Sift4G

Benign

0.14

Polyphen

0.0040

Vest4

0.053

MVP

0.082

MPC

0.25

ClinPred

0.10

GERP RS

4.1

Varity_R

0.058

gMVP

0.14

Mutation Taster

=73/27

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over