Genetic Variant ARHGEF12:c.3277+144G>A (chr11-120475651-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015313.3(ARHGEF12):c.3277+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 846,110 control chromosomes in the GnomAD database, including 14,076 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 0.20 ( 3118 hom., cov: 32)

Exomes 𝑓: 0.17 ( 10958 hom. )

Consequence

ARHGEF12
NM_015313.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

Publications

12 publications found

Variant links:

Genes affected

ARHGEF12 (HGNC:14193): (Rho guanine nucleotide exchange factor 12) Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli working through G protein-coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein has been observed to form a myeloid/lymphoid fusion partner in acute myeloid leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

ARHGEF12 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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015313.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGEF12	NM_015313.3	MANE Select	c.3277+144G>A	intron	N/A	NP_056128.1
ARHGEF12	NM_001198665.2		c.3220+144G>A	intron	N/A	NP_001185594.1
ARHGEF12	NM_001301084.2		c.2968+144G>A	intron	N/A	NP_001288013.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGEF12	ENST00000397843.7	TSL:1 MANE Select	c.3277+144G>A	intron	N/A	ENSP00000380942.2
ARHGEF12	ENST00000532993.5	TSL:1	c.2968+144G>A	intron	N/A	ENSP00000432984.1
ARHGEF12	ENST00000356641.7	TSL:5	c.3220+144G>A	intron	N/A	ENSP00000349056.3

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29826

AN:

151954

Hom.:

3113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.0451

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.235

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.162

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.172

AC:

119139

AN:

694038

Hom.:

10958

AF XY:

0.172

AC XY:

60515

AN XY:

351458

show subpopulations

African (AFR)

AF:

0.246

AC:

3981

AN:

16208

American (AMR)

AF:

0.186

AC:

3079

AN:

16588

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

2531

AN:

14468

East Asian (EAS)

AF:

0.224

AC:

6966

AN:

31078

South Asian (SAS)

AF:

0.212

AC:

8267

AN:

39010

European-Finnish (FIN)

AF:

0.226

AC:

7590

AN:

33632

Middle Eastern (MID)

AF:

0.153

AC:

483

AN:

3150

European-Non Finnish (NFE)

AF:

0.159

AC:

80403

AN:

506564

Other (OTH)

AF:

0.175

AC:

5839

AN:

33340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

4702

9404

14107

18809

23511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2278

4556

6834

9112

11390

<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:

0.196

AC:

29855

AN:

152072

Hom.:

3118

Cov.:

AF XY:

0.200

AC XY:

14868

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.247

AC:

10247

AN:

41474

American (AMR)

AF:

0.177

AC:

2699

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

597

AN:

3468

East Asian (EAS)

AF:

0.235

AC:

1214

AN:

5174

South Asian (SAS)

AF:

0.233

AC:

1122

AN:

4812

European-Finnish (FIN)

AF:

0.237

AC:

2500

AN:

10568

Middle Eastern (MID)

AF:

0.161

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.162

AC:

11037

AN:

67994

Other (OTH)

AF:

0.167

AC:

351

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1200

2400

3601

4801

6001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.173

Hom.:

7460

Bravo

AF:

0.192

Asia WGS

AF:

0.273

AC:

947

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.4

(source)

DANN

Benign

0.68

PhyloP100

-0.010

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