Genetic Variant NM_001242409.2:c.262+84A>G (chr18-32392811-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.262+84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,431,734 control chromosomes in the GnomAD database, including 182,449 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 0.39 ( 14416 hom., cov: 32)

Exomes 𝑓: 0.50 ( 168033 hom. )

Consequence

GAREM1
NM_001242409.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0450

Publications

9 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 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.262+84A>G		intron	N/A	NP_001229338.1	Q9H706-1
	GAREM1	NM_022751.3		c.262+84A>G		intron	N/A	NP_073588.1	Q9H706-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GAREM1	ENST00000269209.7	TSL:1 MANE Select	c.262+84A>G	intron	N/A	ENSP00000269209.6	Q9H706-1
GAREM1	ENST00000399218.8	TSL:2	c.262+84A>G	intron	N/A	ENSP00000382165.3	Q9H706-3
GAREM1	ENST00000952372.1		c.262+84A>G	intron	N/A	ENSP00000622431.1

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59367

AN:

152010

Hom.:

14418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0969

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.297

Gnomad SAS

AF:

0.444

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.426

GnomAD4 exome

AF:

0.505

AC:

646059

AN:

1279606

Hom.:

168033

AF XY:

0.505

AC XY:

320881

AN XY:

634918

show subpopulations

African (AFR)

AF:

0.0827

AC:

2453

AN:

29654

American (AMR)

AF:

0.398

AC:

15310

AN:

38486

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

11387

AN:

22032

East Asian (EAS)

AF:

0.313

AC:

11938

AN:

38128

South Asian (SAS)

AF:

0.454

AC:

32557

AN:

71774

European-Finnish (FIN)

AF:

0.535

AC:

27075

AN:

50570

Middle Eastern (MID)

AF:

0.539

AC:

2834

AN:

5256

European-Non Finnish (NFE)

AF:

0.533

AC:

516647

AN:

970180

Other (OTH)

AF:

0.483

AC:

25858

AN:

53526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

14682

29364

44046

58728

73410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14440

28880

43320

57760

72200

<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:

0.390

AC:

59356

AN:

152128

Hom.:

14416

Cov.:

AF XY:

0.392

AC XY:

29126

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0966

AC:

4016

AN:

41560

American (AMR)

AF:

0.428

AC:

6527

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1791

AN:

3470

East Asian (EAS)

AF:

0.297

AC:

1534

AN:

5170

South Asian (SAS)

AF:

0.446

AC:

2153

AN:

4832

European-Finnish (FIN)

AF:

0.532

AC:

5619

AN:

10568

Middle Eastern (MID)

AF:

0.551

AC:

162

AN:

294

European-Non Finnish (NFE)

AF:

0.533

AC:

36217

AN:

67956

Other (OTH)

AF:

0.421

AC:

886

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1600

3200

4799

6399

7999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.493

Hom.:

12497

Bravo

AF:

0.365

Asia WGS

AF:

0.368

AC:

1285

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.2

(source)

DANN

Benign

0.64

PhyloP100

-0.045

Mutation Taster

=100/0

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