dbSNP rs2240567: ARHGAP44:c.387+142C>A (chr17-12916153-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014859.6(ARHGAP44):c.387+142C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 681,856 control chromosomes in the GnomAD database, including 7,961 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 0.16 ( 2934 hom., cov: 32)

Exomes 𝑓: 0.11 ( 5027 hom. )

Consequence

ARHGAP44
NM_014859.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.81

Publications

4 publications found

Variant links:

Genes affected

ARHGAP44 (HGNC:29096): (Rho GTPase activating protein 44) Enables phospholipid binding activity. Predicted to be involved in several processes, including modification of dendritic spine; negative regulation of Rac protein signal transduction; and regulation of plasma membrane bounded cell projection organization. Located in leading edge membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGAP44 links:

Genome browser will be placed here

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014859.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGAP44	NM_014859.6	MANE Select	c.387+142C>A	intron	N/A	NP_055674.4
ARHGAP44	NM_001321166.2		c.387+142C>A	intron	N/A	NP_001308095.1
ARHGAP44	NM_001321167.2		c.387+142C>A	intron	N/A	NP_001308096.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ARHGAP44	ENST00000379672.10	TSL:1 MANE Select	c.387+142C>A	intron	N/A	ENSP00000368994.5
ARHGAP44	ENST00000340825.7	TSL:1	c.387+142C>A	intron	N/A	ENSP00000342566.3
ARHGAP44	ENST00000262444.13	TSL:1	c.387+142C>A	intron	N/A	ENSP00000262444.9

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24692

AN:

151956

Hom.:

2927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.323

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.363

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.0833

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0720

Gnomad OTH

AF:

0.147

GnomAD4 exome

AF:

0.108

AC:

57283

AN:

529782

Hom.:

5027

AF XY:

0.109

AC XY:

30251

AN XY:

277854

show subpopulations

African (AFR)

AF:

0.327

AC:

4483

AN:

13714

American (AMR)

AF:

0.144

AC:

2852

AN:

19842

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

1873

AN:

14186

East Asian (EAS)

AF:

0.374

AC:

11610

AN:

31054

South Asian (SAS)

AF:

0.146

AC:

6804

AN:

46540

European-Finnish (FIN)

AF:

0.0800

AC:

3322

AN:

41516

Middle Eastern (MID)

AF:

0.0951

AC:

200

AN:

2102

European-Non Finnish (NFE)

AF:

0.0690

AC:

22962

AN:

332650

Other (OTH)

AF:

0.113

AC:

3177

AN:

28178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2242

4484

6727

8969

11211

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.163

AC:

24718

AN:

152074

Hom.:

2934

Cov.:

AF XY:

0.163

AC XY:

12131

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.323

AC:

13388

AN:

41418

American (AMR)

AF:

0.135

AC:

2066

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.140

AC:

485

AN:

3470

East Asian (EAS)

AF:

0.364

AC:

1873

AN:

5144

South Asian (SAS)

AF:

0.162

AC:

781

AN:

4828

European-Finnish (FIN)

AF:

0.0833

AC:

884

AN:

10614

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0720

AC:

4897

AN:

68006

Other (OTH)

AF:

0.147

AC:

311

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

958

1917

2875

3834

4792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<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:

0.103

Hom.:

4866

Bravo

AF:

0.174

Asia WGS

AF:

0.239

AC:

829

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.20

(source)

DANN

Benign

0.45

PhyloP100

-1.8

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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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