Genetic Variant ARHGAP32:c.1976+144T>C (chr11-128980409-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001378024.1(ARHGAP32):c.1976+144T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 561,186 control chromosomes in the GnomAD database, including 25,815 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 0.28 ( 6284 hom., cov: 32)

Exomes 𝑓: 0.30 ( 19531 hom. )

Consequence

ARHGAP32
NM_001378024.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.449

Publications

1 publications found

Variant links:

Genes affected

ARHGAP32 (HGNC:17399): (Rho GTPase activating protein 32) RICS is a neuron-associated GTPase-activating protein that may regulate dendritic spine morphology and strength by modulating Rho GTPase (see RHOA; MIM 165390) activity (Okabe et al., 2003 [PubMed 12531901]).[supplied by OMIM, Mar 2008]

ARHGAP32 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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378024.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGAP32	NM_001378024.1	MANE Select	c.1976+144T>C	intron	N/A	NP_001364953.1
ARHGAP32	NM_001142685.2		c.1934+144T>C	intron	N/A	NP_001136157.1
ARHGAP32	NM_001378025.1		c.1814+144T>C	intron	N/A	NP_001364954.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGAP32	ENST00000682385.1	MANE Select	c.1976+144T>C	intron	N/A	ENSP00000507720.1
ARHGAP32	ENST00000310343.13	TSL:1	c.1934+144T>C	intron	N/A	ENSP00000310561.8
ARHGAP32	ENST00000392657.7	TSL:1	c.887+144T>C	intron	N/A	ENSP00000376425.3

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

41913

AN:

152078

Hom.:

6283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.280

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.374

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.322

GnomAD4 exome

AF:

0.302

AC:

123312

AN:

408990

Hom.:

19531

AF XY:

0.298

AC XY:

63464

AN XY:

212800

show subpopulations

African (AFR)

AF:

0.183

AC:

1923

AN:

10500

American (AMR)

AF:

0.360

AC:

4774

AN:

13262

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

4319

AN:

12210

East Asian (EAS)

AF:

0.283

AC:

7860

AN:

27764

South Asian (SAS)

AF:

0.174

AC:

5201

AN:

29830

European-Finnish (FIN)

AF:

0.223

AC:

6843

AN:

30620

Middle Eastern (MID)

AF:

0.376

AC:

672

AN:

1788

European-Non Finnish (NFE)

AF:

0.325

AC:

84282

AN:

259368

Other (OTH)

AF:

0.315

AC:

7438

AN:

23648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3986

7971

11957

15942

19928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.275

AC:

41924

AN:

152196

Hom.:

6284

Cov.:

AF XY:

0.270

AC XY:

20066

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.181

AC:

7507

AN:

41522

American (AMR)

AF:

0.352

AC:

5382

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

1299

AN:

3472

East Asian (EAS)

AF:

0.310

AC:

1609

AN:

5186

South Asian (SAS)

AF:

0.166

AC:

800

AN:

4828

European-Finnish (FIN)

AF:

0.215

AC:

2277

AN:

10596

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.323

AC:

21991

AN:

68000

Other (OTH)

AF:

0.324

AC:

685

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1531

3063

4594

6126

7657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.280

Hom.:

1049

Bravo

AF:

0.287

Asia WGS

AF:

0.210

AC:

730

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.8

(source)

DANN

Benign

0.67

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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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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