Variant 19-1068735-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_012292.5(ARHGAP45):c.412T>C(p.Leu138=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,610,260 control chromosomes in the GnomAD database, including 113,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 13110 hom., cov: 32)

Exomes 𝑓: 0.37 ( 99990 hom. )

Consequence

ARHGAP45
NM_012292.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

ARHGAP45 (HGNC:17102): (Rho GTPase activating protein 45) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP45 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-1068735-T-C is Benign according to our data. Variant chr19-1068735-T-C is described in ClinVar as [Benign]. Clinvar id is 1262943.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP45	NM_012292.5 linkuse as main transcript	c.412T>C	p.Leu138=	synonymous_variant	2/23	ENST00000313093.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP45	ENST00000313093.7 linkuse as main transcript	c.412T>C	p.Leu138=	synonymous_variant	2/23	1	NM_012292.5	P3	Q92619-1

Frequencies

GnomAD3 genomes

AF:

0.410

AC:

62129

AN:

151400

Hom.:

13077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.350

Gnomad SAS

AF:

0.364

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.391

GnomAD3 exomes

AF:

0.379

AC:

90353

AN:

238622

Hom.:

17470

AF XY:

0.376

AC XY:

49065

AN XY:

130540

show subpopulations

Gnomad AFR exome

AF:

0.526

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.338

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.359

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.368

AC:

536245

AN:

1458742

Hom.:

99990

Cov.:

AF XY:

0.368

AC XY:

266758

AN XY:

725614

show subpopulations

Gnomad4 AFR exome

AF:

0.517

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.315

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.386

Gnomad4 FIN exome

AF:

0.361

Gnomad4 NFE exome

AF:

0.362

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.411

AC:

62208

AN:

151518

Hom.:

13110

Cov.:

AF XY:

0.412

AC XY:

30452

AN XY:

74000

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.413

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.349

Gnomad4 SAS

AF:

0.365

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.385

Alfa

AF:

0.379

Hom.:

5712

Bravo

AF:

0.420

Asia WGS

AF:

0.351

AC:

1217

AN:

3478

EpiCase

AF:

0.363

EpiControl

AF:

0.356

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

GeneDx

Dec 30, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.4

DANN

Benign

0.78

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