Genetic Variant NM_012292.5:c.*38T>C (chr19-1086044-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012292.5(ARHGAP45):c.*38T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 1,549,448 control chromosomes in the GnomAD database, including 140,622 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 10528 hom., cov: 32)

Exomes 𝑓: 0.42 ( 130094 hom. )

Consequence

ARHGAP45
NM_012292.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Publications

23 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP45	NM_012292.5 link	c.*38T>C		3_prime_UTR_variant	Exon 23 of 23	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.*38T>C		3_prime_UTR_variant	Exon 23 of 23	1	NM_012292.5	ENSP00000316772.2		Q92619-1

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

52012

AN:

151920

Hom.:

10536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.395

AC:

89181

AN:

225562

AF XY:

0.397

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.513

Gnomad EAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.455

Gnomad NFE exome

AF:

0.456

Gnomad OTH exome

AF:

0.424

GnomAD4 exome

AF:

0.424

AC:

592990

AN:

1397408

Hom.:

130094

Cov.:

AF XY:

0.422

AC XY:

293229

AN XY:

694486

show subpopulations

African (AFR)

AF:

0.122

AC:

3928

AN:

32222

American (AMR)

AF:

0.451

AC:

19573

AN:

43430

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

12232

AN:

24108

East Asian (EAS)

AF:

0.145

AC:

5694

AN:

39212

South Asian (SAS)

AF:

0.321

AC:

26136

AN:

81368

European-Finnish (FIN)

AF:

0.457

AC:

23201

AN:

50748

Middle Eastern (MID)

AF:

0.498

AC:

2743

AN:

5512

European-Non Finnish (NFE)

AF:

0.448

AC:

476277

AN:

1062710

Other (OTH)

AF:

0.399

AC:

23206

AN:

58098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

16985

33970

50956

67941

84926

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.342

AC:

51991

AN:

152040

Hom.:

10528

Cov.:

AF XY:

0.341

AC XY:

25305

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.130

AC:

5406

AN:

41502

American (AMR)

AF:

0.419

AC:

6406

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

1765

AN:

3470

East Asian (EAS)

AF:

0.142

AC:

731

AN:

5164

South Asian (SAS)

AF:

0.318

AC:

1535

AN:

4824

European-Finnish (FIN)

AF:

0.446

AC:

4717

AN:

10568

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.446

AC:

30264

AN:

67930

Other (OTH)

AF:

0.369

AC:

776

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1650

3300

4950

6600

8250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.425

Hom.:

22809

Bravo

AF:

0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.095

(source)

DANN

Benign

0.36

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_012292.5:c.*38T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over