Genetic Variant ARHGAP6:c.589-10dupT (chrX-11254716-C-CA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_013427.3(ARHGAP6):c.589-10dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.080 ( 92 hom., 185 hem., cov: 19)

Exomes 𝑓: 0.021 ( 2 hom. 14 hem. )

Consequence

ARHGAP6
NM_013427.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

0 publications found

Variant links:

Genes affected

ARHGAP6 (HGNC:676): (Rho GTPase activating protein 6) This gene encodes a member of the rhoGAP family of proteins which play a role in the regulation of actin polymerization at the plasma membrane during several cellular processes. This protein is thought to have two independent functions, one as a GTPase-activating protein with specificity for RhoA, and another as a cytoskeletal protein that promotes actin remodeling. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ARHGAP6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP6	NM_013427.3 link	c.589-10dupT		intron_variant	Intron 1 of 12	ENST00000337414.9	NP_038286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP6	ENST00000337414.9 link	c.589-10_589-9insT		intron_variant	Intron 1 of 12	1	NM_013427.3	ENSP00000338967.4

Frequencies

GnomAD3 genomes

AF:

0.0801

AC:

2784

AN:

34775

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.0215

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0596

Gnomad FIN

AF:

0.0362

Gnomad MID

AF:

0.118

Gnomad NFE

AF:

0.0661

Gnomad OTH

AF:

0.105

GnomAD2 exomes

AF:

0.0379

AC:

569

AN:

15013

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0518

Gnomad AMR exome

AF:

0.0695

Gnomad ASJ exome

AF:

0.0573

Gnomad EAS exome

AF:

0.0515

Gnomad FIN exome

AF:

0.00361

Gnomad NFE exome

AF:

0.0314

Gnomad OTH exome

AF:

0.0442

GnomAD4 exome

AF:

0.0215

AC:

17218

AN:

801808

Hom.:

Cov.:

AF XY:

0.0000642

AC XY:

AN XY:

218190

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0228

AC:

418

AN:

18348

American (AMR)

AF:

0.0567

AC:

556

AN:

9811

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

210

AN:

10730

East Asian (EAS)

AF:

0.0203

AC:

429

AN:

21084

South Asian (SAS)

AF:

0.0216

AC:

403

AN:

18623

European-Finnish (FIN)

AF:

0.0116

AC:

250

AN:

21523

Middle Eastern (MID)

AF:

0.0209

AC:

AN:

1915

European-Non Finnish (NFE)

AF:

0.0213

AC:

14201

AN:

666731

Other (OTH)

AF:

0.0215

AC:

711

AN:

33043

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.287

Heterozygous variant carriers

1324

2648

3971

5295

6619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

676

1352

2028

2704

3380

<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:

0.0799

AC:

2778

AN:

34773

Hom.:

Cov.:

AF XY:

0.0320

AC XY:

185

AN XY:

5787

show subpopulations

African (AFR)

AF:

0.0576

AC:

527

AN:

9148

American (AMR)

AF:

0.222

AC:

728

AN:

3275

Ashkenazi Jewish (ASJ)

AF:

0.102

AC:

AN:

931

East Asian (EAS)

AF:

0.104

AC:

114

AN:

1098

South Asian (SAS)

AF:

0.0571

AC:

AN:

631

European-Finnish (FIN)

AF:

0.0362

AC:

AN:

1105

Middle Eastern (MID)

AF:

0.0968

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0660

AC:

1181

AN:

17882

Other (OTH)

AF:

0.103

AC:

AN:

455

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

184

275

367

459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0154

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.085

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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X-11254716-CAAAAAAAAAAAA-CAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over