Genetic Variant ARHGAP45:c.-80C>T (chr19-1065946-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000539243.6(ARHGAP45):c.-80C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,483,714 control chromosomes in the GnomAD database, including 28,530 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 0.17 ( 2699 hom., cov: 34)

Exomes 𝑓: 0.19 ( 25831 hom. )

Consequence

ARHGAP45
ENST00000539243.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.26

Publications

15 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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new If you want to explore the variant's impact on the transcript ENST00000539243.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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 (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539243.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP45	NM_001258328.4		c.-80C>T		upstream_gene	N/A	NP_001245257.1	Q92619-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP45	ENST00000539243.6	TSL:2	c.-80C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 23	ENSP00000439601.1	Q92619-2
	ARHGAP45	ENST00000539243.6	TSL:2	c.-80C>T		5_prime_UTR	Exon 1 of 23	ENSP00000439601.1	Q92619-2

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25420

AN:

152150

Hom.:

2689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0438

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.321

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.191

AC:

254342

AN:

1331446

Hom.:

25831

Cov.:

AF XY:

0.193

AC XY:

125786

AN XY:

651744

show subpopulations

African (AFR)

AF:

0.0339

AC:

1023

AN:

30140

American (AMR)

AF:

0.320

AC:

9442

AN:

29534

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

3757

AN:

21696

East Asian (EAS)

AF:

0.323

AC:

11418

AN:

35310

South Asian (SAS)

AF:

0.241

AC:

17244

AN:

71572

European-Finnish (FIN)

AF:

0.229

AC:

7231

AN:

31556

Middle Eastern (MID)

AF:

0.185

AC:

720

AN:

3894

European-Non Finnish (NFE)

AF:

0.183

AC:

192889

AN:

1052274

Other (OTH)

AF:

0.191

AC:

10618

AN:

55470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

10535

21069

31604

42138

52673

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6966

13932

20898

27864

34830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.167

AC:

25427

AN:

152268

Hom.:

2699

Cov.:

AF XY:

0.176

AC XY:

13090

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0437

AC:

1815

AN:

41560

American (AMR)

AF:

0.267

AC:

4083

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

583

AN:

3472

East Asian (EAS)

AF:

0.321

AC:

1663

AN:

5180

South Asian (SAS)

AF:

0.228

AC:

1102

AN:

4830

European-Finnish (FIN)

AF:

0.257

AC:

2726

AN:

10604

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12895

AN:

68004

Other (OTH)

AF:

0.164

AC:

346

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1087

2174

3260

4347

5434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.170

Hom.:

4201

Bravo

AF:

0.163

Asia WGS

AF:

0.258

AC:

895

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.40

(source)

DANN

Benign

0.43

PhyloP100

-4.3

PromoterAI

-0.056

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over