dbSNP rs2274788: ARHGAP29:c.437+84A>G (chr1-94209170-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004815.4(ARHGAP29):c.437+84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,024,554 control chromosomes in the GnomAD database, including 31,147 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 0.20 ( 3595 hom., cov: 32)

Exomes 𝑓: 0.25 ( 27552 hom. )

Consequence

ARHGAP29
NM_004815.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.296

Publications

11 publications found

Variant links:

Genes affected

ARHGAP29 (HGNC:30207): (Rho GTPase activating protein 29) Rap1 is a small GTPase that, through effectors, regulates Rho GTPase signaling. These effectors- Rasip1, Radil, and the protein encoded by this gene- translocate to the cell membrane, where they form a multiprotein complex. This complex is necessary for Rap1-induced inhibition of Rho signaling. Defects in this gene may be a cause of nonsyndromic cleft lip with or without cleft palate. [provided by RefSeq, Jun 2016]

ARHGAP29 Gene-Disease associations (from GenCC):

cleft lip with or without cleft palate
Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina

ARHGAP29 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=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP29	NM_004815.4 link	c.437+84A>G		intron_variant	Intron 4 of 22	ENST00000260526.11	NP_004806.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ARHGAP29	ENST00000260526.11 link	c.437+84A>G	intron_variant	Intron 4 of 22	1	NM_004815.4	ENSP00000260526.6
ARHGAP29	ENST00000370217.3 link	c.437+84A>G	intron_variant	Intron 4 of 10	1		ENSP00000359237.3
ARHGAP29	ENST00000552844.5 link	n.437+84A>G	intron_variant	Intron 4 of 25	1		ENSP00000449764.1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30307

AN:

152052

Hom.:

3599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0660

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.245

AC:

214109

AN:

872384

Hom.:

27552

AF XY:

0.245

AC XY:

110923

AN XY:

452820

show subpopulations

African (AFR)

AF:

0.0600

AC:

1226

AN:

20436

American (AMR)

AF:

0.220

AC:

5703

AN:

25944

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

5554

AN:

20536

East Asian (EAS)

AF:

0.296

AC:

10747

AN:

36318

South Asian (SAS)

AF:

0.193

AC:

12513

AN:

64776

European-Finnish (FIN)

AF:

0.203

AC:

9857

AN:

48550

Middle Eastern (MID)

AF:

0.249

AC:

1106

AN:

4450

European-Non Finnish (NFE)

AF:

0.258

AC:

157836

AN:

610870

Other (OTH)

AF:

0.236

AC:

9567

AN:

40504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

7926

15852

23779

31705

39631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3876

7752

11628

15504

19380

<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:

0.199

AC:

30291

AN:

152170

Hom.:

3595

Cov.:

AF XY:

0.199

AC XY:

14773

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0658

AC:

2733

AN:

41532

American (AMR)

AF:

0.237

AC:

3627

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

882

AN:

3466

East Asian (EAS)

AF:

0.325

AC:

1678

AN:

5170

South Asian (SAS)

AF:

0.185

AC:

889

AN:

4816

European-Finnish (FIN)

AF:

0.213

AC:

2258

AN:

10594

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.257

AC:

17473

AN:

67984

Other (OTH)

AF:

0.215

AC:

454

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1191

2381

3572

4762

5953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.236

Hom.:

12296

Bravo

AF:

0.198

Asia WGS

AF:

0.203

AC:

707

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.55

PhyloP100

0.30

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over