dbSNP rs2072254: ARHGAP44:p.Gly288Gly (chr17-12949142-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_014859.6(ARHGAP44):c.864A>G(p.Gly288Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,564,524 control chromosomes in the GnomAD database, including 7,279 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.082 ( 593 hom., cov: 32)

Exomes 𝑓: 0.092 ( 6686 hom. )

Consequence

ARHGAP44
NM_014859.6 splice_region, synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

15 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP44	NM_014859.6 link	c.864A>G	p.Gly288Gly	splice_region_variant, synonymous_variant	Exon 11 of 21	ENST00000379672.10	NP_055674.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP44	ENST00000379672.10 link	c.864A>G	p.Gly288Gly	splice_region_variant, synonymous_variant	Exon 11 of 21	1	NM_014859.6	ENSP00000368994.5

Frequencies

GnomAD3 genomes

AF:

0.0816

AC:

12384

AN:

151752

Hom.:

595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0531

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0510

Gnomad MID

AF:

0.0860

Gnomad NFE

AF:

0.0884

Gnomad OTH

AF:

0.0761

GnomAD2 exomes

AF:

0.0969

AC:

17092

AN:

176474

AF XY:

0.0977

show subpopulations

Gnomad AFR exome

AF:

0.0408

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.0521

Gnomad EAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.0463

Gnomad NFE exome

AF:

0.0824

Gnomad OTH exome

AF:

0.0934

GnomAD4 exome

AF:

0.0925

AC:

130653

AN:

1412654

Hom.:

6686

Cov.:

AF XY:

0.0939

AC XY:

65546

AN XY:

698050

show subpopulations

African (AFR)

AF:

0.0435

AC:

1401

AN:

32170

American (AMR)

AF:

0.135

AC:

5032

AN:

37216

Ashkenazi Jewish (ASJ)

AF:

0.0509

AC:

1287

AN:

25290

East Asian (EAS)

AF:

0.184

AC:

6736

AN:

36648

South Asian (SAS)

AF:

0.131

AC:

10504

AN:

79922

European-Finnish (FIN)

AF:

0.0507

AC:

2538

AN:

50100

Middle Eastern (MID)

AF:

0.0731

AC:

418

AN:

5720

European-Non Finnish (NFE)

AF:

0.0892

AC:

96929

AN:

1086868

Other (OTH)

AF:

0.0989

AC:

5808

AN:

58720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6093

12185

18278

24370

30463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3680

7360

11040

14720

18400

<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:

0.0816

AC:

12390

AN:

151870

Hom.:

593

Cov.:

AF XY:

0.0818

AC XY:

6068

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.0476

AC:

1972

AN:

41394

American (AMR)

AF:

0.118

AC:

1805

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0531

AC:

184

AN:

3468

East Asian (EAS)

AF:

0.188

AC:

964

AN:

5138

South Asian (SAS)

AF:

0.138

AC:

664

AN:

4806

European-Finnish (FIN)

AF:

0.0510

AC:

538

AN:

10548

Middle Eastern (MID)

AF:

0.0890

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0884

AC:

6007

AN:

67950

Other (OTH)

AF:

0.0786

AC:

165

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

596

1193

1789

2386

2982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0788

Hom.:

425

Bravo

AF:

0.0846

Asia WGS

AF:

0.177

AC:

614

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.3

(source)

DANN

Benign

0.79

PhyloP100

-1.1

Mutation Taster

=97/3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over