Genetic Variant NM_012292.5:c.422-1836C>T (chr19-1071313-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012292.5(ARHGAP45):c.422-1836C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,445,214 control chromosomes in the GnomAD database, including 360,670 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36512 hom., cov: 32)

Exomes 𝑓: 0.71 ( 324158 hom. )

Consequence

ARHGAP45
NM_012292.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.153

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2738469E-6).

BP6

Variant 19-1071313-C-T is Benign according to our data. Variant chr19-1071313-C-T is described in ClinVar as [Benign]. Clinvar id is 1257224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP45	NM_012292.5 link	c.422-1836C>T		intron_variant	Intron 2 of 22	ENST00000313093.7	NP_036424.2	Q92619-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP45	ENST00000313093.7 link	c.422-1836C>T		intron_variant	Intron 2 of 22	1	NM_012292.5	ENSP00000316772.2		Q92619-1

Frequencies

GnomAD3 genomes

AF:

0.691

AC:

104549

AN:

151254

Hom.:

36480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.672

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.765

Gnomad ASJ

AF:

0.698

Gnomad EAS

AF:

0.449

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.702

Gnomad MID

AF:

0.776

Gnomad NFE

AF:

0.712

Gnomad OTH

AF:

0.694

GnomAD3 exomes

AF:

0.774

AC:

46667

AN:

60272

Hom.:

18091

AF XY:

0.762

AC XY:

26853

AN XY:

35232

show subpopulations

Gnomad AFR exome

AF:

0.741

Gnomad AMR exome

AF:

0.878

Gnomad ASJ exome

AF:

0.734

Gnomad EAS exome

AF:

0.580

Gnomad SAS exome

AF:

0.718

Gnomad FIN exome

AF:

0.757

Gnomad NFE exome

AF:

0.772

Gnomad OTH exome

AF:

0.794

GnomAD4 exome

AF:

0.706

AC:

912839

AN:

1293852

Hom.:

324158

Cov.:

AF XY:

0.705

AC XY:

449459

AN XY:

637214

show subpopulations

Gnomad4 AFR exome

AF:

0.674

Gnomad4 AMR exome

AF:

0.844

Gnomad4 ASJ exome

AF:

0.699

Gnomad4 EAS exome

AF:

0.435

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.711

Gnomad4 NFE exome

AF:

0.714

Gnomad4 OTH exome

AF:

0.690

GnomAD4 genome

AF:

0.691

AC:

104619

AN:

151362

Hom.:

36512

Cov.:

AF XY:

0.689

AC XY:

50932

AN XY:

73966

show subpopulations

Gnomad4 AFR

AF:

0.672

Gnomad4 AMR

AF:

0.766

Gnomad4 ASJ

AF:

0.698

Gnomad4 EAS

AF:

0.448

Gnomad4 SAS

AF:

0.606

Gnomad4 FIN

AF:

0.702

Gnomad4 NFE

AF:

0.712

Gnomad4 OTH

AF:

0.685

Alfa

AF:

0.694

Hom.:

4560

Bravo

AF:

0.697

TwinsUK

AF:

0.698

AC:

2589

ALSPAC

AF:

0.712

AC:

2743

ExAC

AF:

0.645

AC:

7440

Asia WGS

AF:

0.509

AC:

1754

AN:

3442

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0084

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0000013

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.72

REVEL

Benign

0.0050

Sift

Benign

0.52

Sift4G

Benign

0.11

Polyphen

0.17

Vest4

0.070

ClinPred

0.0021

GERP RS

0.84

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