4-85994695-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001025616.3(ARHGAP24):c.1041T>C(p.Asn347Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,613,714 control chromosomes in the GnomAD database, including 53,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7653 hom., cov: 31)

Exomes 𝑓: 0.24 ( 45746 hom. )

Consequence

ARHGAP24
NM_001025616.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.493

Publications

12 publications found

Variant links:

Genes affected

ARHGAP24 (HGNC:25361): (Rho GTPase activating protein 24) This gene encodes a Rho-GTPase activating protein, which is specific for the small GTPase family member Rac. Binding of the encoded protein by filamin A targets it to sites of membrane protrusion, where it antognizes Rac. This results in suppression of lamellae formation and promotion of retraction to regulate cell polarity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ARHGAP24 links:

MAPK10 (HGNC:6872): (mitogen-activated protein kinase 10) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as integration points for multiple biochemical signals, and thus are involved in a wide variety of cellular processes, such as proliferation, differentiation, transcription regulation and development. This kinase is specifically expressed in a subset of neurons in the nervous system, and is activated by threonine and tyrosine phosphorylation. Targeted deletion of this gene in mice suggests that it may have a role in stress-induced neuronal apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]

MAPK10 Gene-Disease associations (from GenCC):

Lennox-Gastaut syndrome
Inheritance: AD Classification: LIMITED Submitted by: G2P

MAPK10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 4-85994695-T-C is Benign according to our data. Variant chr4-85994695-T-C is described in ClinVar as [Benign]. Clinvar id is 1268964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.493 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP24	NM_001025616.3 link	c.1041T>C	p.Asn347Asn	synonymous_variant	Exon 9 of 10	ENST00000395184.6	NP_001020787.2	Q8N264-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP24	ENST00000395184.6 link	c.1041T>C	p.Asn347Asn	synonymous_variant	Exon 9 of 10	2	NM_001025616.3	ENSP00000378611.1		Q8N264-1

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45596

AN:

151740

Hom.:

7645

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.257

GnomAD2 exomes

AF:

0.281

AC:

70570

AN:

251066

AF XY:

0.279

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.356

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.238

Gnomad NFE exome

AF:

0.221

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.243

AC:

354862

AN:

1461856

Hom.:

45746

Cov.:

AF XY:

0.246

AC XY:

178871

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.453

AC:

15151

AN:

33476

American (AMR)

AF:

0.348

AC:

15555

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

5410

AN:

26134

East Asian (EAS)

AF:

0.281

AC:

11152

AN:

39700

South Asian (SAS)

AF:

0.385

AC:

33218

AN:

86258

European-Finnish (FIN)

AF:

0.234

AC:

12478

AN:

53416

Middle Eastern (MID)

AF:

0.242

AC:

1395

AN:

5768

European-Non Finnish (NFE)

AF:

0.221

AC:

245204

AN:

1111994

Other (OTH)

AF:

0.253

AC:

15299

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

18430

36859

55289

73718

92148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.301

AC:

45646

AN:

151858

Hom.:

7653

Cov.:

AF XY:

0.306

AC XY:

22670

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.454

AC:

18799

AN:

41390

American (AMR)

AF:

0.300

AC:

4590

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

703

AN:

3470

East Asian (EAS)

AF:

0.284

AC:

1458

AN:

5142

South Asian (SAS)

AF:

0.397

AC:

1904

AN:

4798

European-Finnish (FIN)

AF:

0.236

AC:

2489

AN:

10532

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14973

AN:

67940

Other (OTH)

AF:

0.256

AC:

538

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1556

3111

4667

6222

7778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.253

Hom.:

4355

Bravo

AF:

0.308

Asia WGS

AF:

0.370

AC:

1285

AN:

3478

EpiCase

AF:

0.218

EpiControl

AF:

0.215

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.091

(source)

DANN

Benign

0.61

PhyloP100

-0.49

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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4-85994695-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over