dbSNP rs3744921: GAREM1:p.Lys291Arg (chr18-32287725-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAREM1	NM_001242409.2 link	c.872A>G	p.Lys291Arg	missense_variant	Exon 4 of 6	ENST00000269209.7	NP_001229338.1	Q9H706-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GAREM1	ENST00000269209.7 link	c.872A>G	p.Lys291Arg	missense_variant	Exon 4 of 6	1	NM_001242409.2	ENSP00000269209.6	Q9H706-1
GAREM1	ENST00000399218.8 link	c.872A>G	p.Lys291Arg	missense_variant	Exon 4 of 6	2		ENSP00000382165.3	Q9H706-3
ENSG00000264982	ENST00000579580.1 link	n.289T>C		non_coding_transcript_exon_variant	Exon 1 of 2	3
GAREM1	ENST00000578619.1 link	n.*151A>G		downstream_gene_variant		4

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

GnomAD3 exomes

AF:

0.0183

AC:

4604

AN:

251482

Hom.:

103

AF XY:

0.0170

AC XY:

2305

AN XY:

135916

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 SAS exome

AF:

0.0294

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

Gnomad4 AFR exome

AF:

0.00804

Gnomad4 AMR exome

AF:

0.0468

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.0870

Gnomad4 SAS exome

AF:

0.0281

Gnomad4 FIN exome

AF:

0.00580

Gnomad4 NFE exome

AF:

0.00462

Gnomad4 OTH exome

AF:

0.0108

GnomAD4 genome

AF:

0.0103

AC:

1570

AN:

152152

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

776

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00858

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.0593

Gnomad4 SAS

AF:

0.0306

Gnomad4 FIN

AF:

0.00669

Gnomad4 NFE

AF:

0.00485

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00861

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

0.0060

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.98

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.051

Sift

Benign

0.22

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0

B;B

Vest4

0.17

MPC

0.20

ClinPred

0.0071

GERP RS

4.5

Varity_R

0.12

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over