Variant 4-147875047-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_024605.4(ARHGAP10):c.729G>A(p.Arg243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 1,604,706 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 34 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 75 hom. )

Consequence

ARHGAP10
NM_024605.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.831

Variant links:

Genes affected

ARHGAP10 (HGNC:26099): (Rho GTPase activating protein 10) Predicted to enable GTPase activator activity. Predicted to be involved in cytoskeleton organization and negative regulation of apoptotic process. Predicted to be located in perinuclear region of cytoplasm and plasma membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 4-147875047-G-A is Benign according to our data. Variant chr4-147875047-G-A is described in ClinVar as [Benign]. Clinvar id is 717842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.831 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0127 (1940/152242) while in subpopulation AFR AF= 0.0422 (1753/41524). AF 95% confidence interval is 0.0406. There are 34 homozygotes in gnomad4. There are 913 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP10	NM_024605.4 linkuse as main transcript	c.729G>A	p.Arg243=	synonymous_variant	8/23	ENST00000336498.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP10	ENST00000336498.8 linkuse as main transcript	c.729G>A	p.Arg243=	synonymous_variant	8/23	1	NM_024605.4	P1
ARHGAP10	ENST00000506054.5 linkuse as main transcript	n.5861G>A		non_coding_transcript_exon_variant	2/17	1

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1930

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0421

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00487

AC:

1185

AN:

243136

Hom.:

AF XY:

0.00438

AC XY:

576

AN XY:

131582

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.0121

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000304

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.00225

AC:

3272

AN:

1452464

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

1697

AN XY:

722466

show subpopulations

Gnomad4 AFR exome

AF:

0.0475

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.0129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000224

Gnomad4 OTH exome

AF:

0.00404

GnomAD4 genome

AF:

0.0127

AC:

1940

AN:

152242

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

913

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0422

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00658

Hom.:

Bravo

AF:

0.0148

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

7.8

DANN

Benign

0.56

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

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