Genetic Variant ARHGEF10:n.197G>A (chr8-1876247-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 ENST00000523711.5(ARHGEF10):n.197G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 381,734 control chromosomes in the GnomAD database, including 11,419 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 0.24 ( 4665 hom., cov: 34)

Exomes 𝑓: 0.23 ( 6754 hom. )

Consequence

ARHGEF10
ENST00000523711.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

Publications

3 publications found

Variant links:

Genes affected

ARHGEF10 (HGNC:14103): (Rho guanine nucleotide exchange factor 10) This gene encodes a Rho guanine nucleotide exchange factor (GEF). Rho GEFs regulate the activity of small Rho GTPases by stimulating the exchange of guanine diphosphate (GDP) for guanine triphosphate (GTP) and may play a role in neural morphogenesis. Mutations in this gene are associated with slowed nerve conduction velocity (SNCV). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ARHGEF10 Gene-Disease associations (from GenCC):

autosomal dominant slowed nerve conduction velocity
Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
hereditary peripheral neuropathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
peripheral neuropathy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ARHGEF10 links:

KBTBD11-OT1 (HGNC:):

KBTBD11-OT1 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 (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGEF10	NM_014629.4 link	c.680-324G>A		intron_variant	Intron 7 of 28	ENST00000349830.8	NP_055444.2	O15013-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGEF10	ENST00000349830.8 link	c.680-324G>A		intron_variant	Intron 7 of 28	1	NM_014629.4	ENSP00000340297.3		O15013-5
KBTBD11-OT1	ENST00000635855.1 link	n.*634-324G>A		intron_variant	Intron 8 of 29	5		ENSP00000489726.1		A0A1B0GTJ5

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36585

AN:

152008

Hom.:

4645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.229

GnomAD4 exome

AF:

0.228

AC:

52450

AN:

229608

Hom.:

6754

Cov.:

AF XY:

0.222

AC XY:

26529

AN XY:

119762

show subpopulations

African (AFR)

AF:

0.193

AC:

1504

AN:

7796

American (AMR)

AF:

0.392

AC:

3336

AN:

8520

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

1326

AN:

7204

East Asian (EAS)

AF:

0.343

AC:

4651

AN:

13568

South Asian (SAS)

AF:

0.159

AC:

4404

AN:

27648

European-Finnish (FIN)

AF:

0.289

AC:

3191

AN:

11032

Middle Eastern (MID)

AF:

0.123

AC:

121

AN:

984

European-Non Finnish (NFE)

AF:

0.222

AC:

31018

AN:

139434

Other (OTH)

AF:

0.216

AC:

2899

AN:

13422

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1880

3760

5641

7521

9401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.241

AC:

36657

AN:

152126

Hom.:

4665

Cov.:

AF XY:

0.244

AC XY:

18122

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.206

AC:

8553

AN:

41508

American (AMR)

AF:

0.337

AC:

5149

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

638

AN:

3468

East Asian (EAS)

AF:

0.359

AC:

1854

AN:

5170

South Asian (SAS)

AF:

0.182

AC:

881

AN:

4830

European-Finnish (FIN)

AF:

0.291

AC:

3071

AN:

10568

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.232

AC:

15786

AN:

67978

Other (OTH)

AF:

0.232

AC:

489

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1468

2936

4404

5872

7340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.237

Hom.:

986

Bravo

AF:

0.248

Asia WGS

AF:

0.289

AC:

1004

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.063

(source)

DANN

Benign

0.67

PhyloP100

-1.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over