Genetic Variant NM_012292.5:c.150C>T (chr19-1068473-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_012292.5(ARHGAP45):c.150C>T(p.Pro50Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,584,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ARHGAP45
NM_012292.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.776

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 19-1068473-C-T is Benign according to our data. Variant chr19-1068473-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 741932.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.776 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012292.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP45	NM_012292.5	MANE Select	c.150C>T	p.Pro50Pro	synonymous	Exon 2 of 23	NP_036424.2
ARHGAP45	NM_001258328.4		c.198C>T	p.Pro66Pro	synonymous	Exon 2 of 23	NP_001245257.1	Q92619-2
ARHGAP45	NM_001321232.2		c.162C>T	p.Pro54Pro	synonymous	Exon 2 of 23	NP_001308161.1	K7ES98

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARHGAP45	ENST00000313093.7	TSL:1 MANE Select	c.150C>T	p.Pro50Pro	synonymous	Exon 2 of 23	ENSP00000316772.2	Q92619-1
ARHGAP45	ENST00000586866.5	TSL:1	c.162C>T	p.Pro54Pro	synonymous	Exon 2 of 23	ENSP00000468615.1	K7ES98
ARHGAP45	ENST00000885660.1		c.150C>T	p.Pro50Pro	synonymous	Exon 2 of 22	ENSP00000555719.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000259

AC:

AN:

193000

AF XY:

0.0000376

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000224

AC:

AN:

1431756

Hom.:

Cov.:

AF XY:

0.0000310

AC XY:

AN XY:

709608

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32736

American (AMR)

AF:

0.00

AC:

AN:

40642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25574

East Asian (EAS)

AF:

0.00

AC:

AN:

37830

South Asian (SAS)

AF:

0.000181

AC:

AN:

82910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50006

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5202

European-Non Finnish (NFE)

AF:

0.0000146

AC:

AN:

1097776

Other (OTH)

AF:

0.0000169

AC:

AN:

59080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000263

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.56

(source)

DANN

Benign

0.72

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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