Variant 2-68813279-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001007231.3(ARHGAP25):c.675-8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000672 in 1,603,174 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 4 hom. )

Consequence

ARHGAP25
NM_001007231.3 splice_region, intron

Scores

Splicing: ADA: 0.0004612

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.776

Variant links:

Genes affected

ARHGAP25 (HGNC:28951): (Rho GTPase activating protein 25) ARHGAPs, such as ARHGAP25, encode negative regulators of Rho GTPases (see ARHA; MIM 165390), which are implicated in actin remodeling, cell polarity, and cell migration (Katoh and Katoh, 2004 [PubMed 15254788]).[supplied by OMIM, Mar 2008]

ARHGAP25 links:

ARHGAP25 (HGNC:):

ARHGAP25 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-68813279-T-C is Benign according to our data. Variant chr2-68813279-T-C is described in ClinVar as [Benign]. Clinvar id is 720549.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP25	NM_001007231.3 linkuse as main transcript	c.675-8T>C		splice_region_variant, intron_variant		ENST00000409202.8	NP_001007232.2	P42331-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP25	ENST00000409202.8 linkuse as main transcript	c.675-8T>C		splice_region_variant, intron_variant		2	NM_001007231.3	ENSP00000386911.3		P42331-4

Frequencies

GnomAD3 genomes

AF:

0.00374

AC:

569

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000888

AC:

212

AN:

238858

Hom.:

AF XY:

0.000726

AC XY:

AN XY:

129518

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.000685

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000347

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000273

Gnomad OTH exome

AF:

0.000348

GnomAD4 exome

AF:

0.000349

AC:

507

AN:

1450886

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

217

AN XY:

722000

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.000830

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000812

Gnomad4 OTH exome

AF:

0.000752

GnomAD4 genome

AF:

0.00374

AC:

570

AN:

152288

Hom.:

Cov.:

AF XY:

0.00385

AC XY:

287

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00412

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 28, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.5

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00046

dbscSNV1_RF

Benign

0.0040

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over