dbSNP rs1541098: ARHGAP29:c.*91A>G (chr1-94202414-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 ENST00000370217.3(ARHGAP29):c.*91A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,087,734 control chromosomes in the GnomAD database, including 29,791 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 0.19 ( 3230 hom., cov: 33)

Exomes 𝑓: 0.23 ( 26561 hom. )

Consequence

ARHGAP29
ENST00000370217.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.251

Publications

7 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP29	NM_004815.4 link	c.1143+130A>G		intron_variant	Intron 11 of 22	ENST00000260526.11	NP_004806.3	Q52LW3-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ARHGAP29	ENST00000370217.3 link	c.*91A>G	3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000359237.3	Q52LW3-2
ARHGAP29	ENST00000260526.11 link	c.1143+130A>G	intron_variant	Intron 11 of 22	1	NM_004815.4	ENSP00000260526.6	Q52LW3-1
ARHGAP29	ENST00000552844.5 link	n.1143+130A>G	intron_variant	Intron 11 of 25	1		ENSP00000449764.1	F8VWZ8

Frequencies

GnomAD3 genomes

AF:

0.186

AC:

28330

AN:

152118

Hom.:

3221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0448

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.185

GnomAD4 exome

AF:

0.235

AC:

219833

AN:

935498

Hom.:

26561

Cov.:

AF XY:

0.232

AC XY:

110397

AN XY:

475186

show subpopulations

African (AFR)

AF:

0.0403

AC:

859

AN:

21296

American (AMR)

AF:

0.286

AC:

7471

AN:

26140

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

3635

AN:

17946

East Asian (EAS)

AF:

0.332

AC:

11894

AN:

35870

South Asian (SAS)

AF:

0.158

AC:

9463

AN:

59776

European-Finnish (FIN)

AF:

0.238

AC:

8248

AN:

34584

Middle Eastern (MID)

AF:

0.135

AC:

611

AN:

4538

European-Non Finnish (NFE)

AF:

0.243

AC:

168518

AN:

692730

Other (OTH)

AF:

0.214

AC:

9134

AN:

42618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

8838

17677

26515

35354

44192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4918

9836

14754

19672

24590

<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:

0.186

AC:

28357

AN:

152236

Hom.:

3230

Cov.:

AF XY:

0.189

AC XY:

14090

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0447

AC:

1856

AN:

41566

American (AMR)

AF:

0.246

AC:

3764

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

708

AN:

3470

East Asian (EAS)

AF:

0.311

AC:

1611

AN:

5172

South Asian (SAS)

AF:

0.153

AC:

739

AN:

4818

European-Finnish (FIN)

AF:

0.246

AC:

2612

AN:

10598

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.243

AC:

16538

AN:

68002

Other (OTH)

AF:

0.186

AC:

394

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1158

2316

3474

4632

5790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.214

Hom.:

9276

Bravo

AF:

0.181

Asia WGS

AF:

0.225

AC:

781

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.21

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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