Genetic Variant NM_001242409.2:c.872A>G (chr18-32287725-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001242409.2(GAREM1):c.872A>G(p.Lys291Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0101 in 1,614,028 control chromosomes in the GnomAD database, including 350 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 0.010 ( 27 hom., cov: 32)

Exomes 𝑓: 0.010 ( 323 hom. )

Consequence

GAREM1
NM_001242409.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.75

Publications

12 publications found

Variant links:

Genes affected

GAREM1 (HGNC:26136): (GRB2 associated regulator of MAPK1 subtype 1) This gene encodes an adaptor protein which functions in the epidermal growth factor (EGF) receptor-mediated signaling pathway. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

GAREM1 links:

ENSG00000264982 (HGNC:):

ENSG00000264982 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022611618).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242409.2. 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
	GAREM1	NM_001242409.2	MANE Select	c.872A>G	p.Lys291Arg	missense	Exon 4 of 6	NP_001229338.1	Q9H706-1
	GAREM1	NM_022751.3		c.872A>G	p.Lys291Arg	missense	Exon 4 of 6	NP_073588.1	Q9H706-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAREM1	ENST00000269209.7	TSL:1 MANE Select	c.872A>G	p.Lys291Arg	missense	Exon 4 of 6	ENSP00000269209.6	Q9H706-1
GAREM1	ENST00000399218.8	TSL:2	c.872A>G	p.Lys291Arg	missense	Exon 4 of 6	ENSP00000382165.3	Q9H706-3
GAREM1	ENST00000952372.1		c.394-17342A>G		intron	N/A	ENSP00000622431.1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1562

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00853

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.0594

Gnomad SAS

AF:

0.0299

Gnomad FIN

AF:

0.00669

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00485

Gnomad OTH

AF:

0.00718

GnomAD2 exomes

AF:

0.0183

AC:

4604

AN:

251482

AF XY:

0.0170

show subpopulations

Gnomad AFR exome

AF:

0.00898

Gnomad AMR exome

AF:

0.0495

Gnomad ASJ exome

AF:

0.0112

Gnomad EAS exome

AF:

0.0510

Gnomad FIN exome

AF:

0.00725

Gnomad NFE exome

AF:

0.00498

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.0101

AC:

14695

AN:

1461876

Hom.:

323

Cov.:

AF XY:

0.0102

AC XY:

7411

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00804

AC:

269

AN:

33478

American (AMR)

AF:

0.0468

AC:

2092

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0111

AC:

289

AN:

26136

East Asian (EAS)

AF:

0.0870

AC:

3452

AN:

39700

South Asian (SAS)

AF:

0.0281

AC:

2423

AN:

86248

European-Finnish (FIN)

AF:

0.00580

AC:

310

AN:

53420

Middle Eastern (MID)

AF:

0.0120

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00462

AC:

5141

AN:

1112006

Other (OTH)

AF:

0.0108

AC:

650

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1081

2162

3243

4324

5405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.0103

AC:

1570

AN:

152152

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

776

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00858

AC:

356

AN:

41504

American (AMR)

AF:

0.0190

AC:

290

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

3470

East Asian (EAS)

AF:

0.0593

AC:

305

AN:

5142

South Asian (SAS)

AF:

0.0306

AC:

147

AN:

4808

European-Finnish (FIN)

AF:

0.00669

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00485

AC:

330

AN:

68026

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

156

235

313

391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00879

Hom.:

Bravo

AF:

0.0129

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.0118

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.0167

AC:

2027

Asia WGS

AF:

0.0560

AC:

195

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.23

Eigen_PC

Benign

0.0060

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0023

MetaSVM

Benign

-0.98

PhyloP100

4.8

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.56

REVEL

Benign

0.051

Sift

Benign

0.22

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.17

MPC

0.20

ClinPred

0.0071

GERP RS

4.5

Varity_R

0.12

gMVP

0.49

Mutation Taster

=97/3

polymorphism (auto)

(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

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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