NM_004815.4:c.206-5292A>G

Variant names:

• chr1-94225684-T-C
• rs3789688
• NM_004815.4:c.206-5292A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004815.4(ARHGAP29):​c.206-5292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,862 control chromosomes in the GnomAD database, including 18,099 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 0.48 (18099 hom., cov: 32)
• Consequence: ARHGAP29 NM_004815.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP29	NM_004815.4	c.206-5292A>G		intron_variant	Intron 2 of 22	ENST00000260526.11	NP_004806.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP29	ENST00000260526.11	c.206-5292A>G		intron_variant	Intron 2 of 22	1	NM_004815.4	ENSP00000260526.6
ARHGAP29	ENST00000370217.3	c.206-5292A>G		intron_variant	Intron 2 of 10	1		ENSP00000359237.3
ARHGAP29	ENST00000552844.5	n.206-5292A>G		intron_variant	Intron 2 of 25	1		ENSP00000449764.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72516 AN: 151744 Hom.: 18107 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.528

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72512 AN: 151862 Hom.: 18099 Cov.: 32 AF XY: 0.470 AC XY: 34883 AN XY: 74216

African (AFR) AF: 0.330 AC: 13675 AN: 41486

American (AMR) AF: 0.484 AC: 7388 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1948 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2390 AN: 5170

South Asian (SAS) AF: 0.403 AC: 1941 AN: 4812

European-Finnish (FIN) AF: 0.490 AC: 5175 AN: 10554

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38052 AN: 67792

Other (OTH) AF: 0.522 AC: 1100 AN: 2106

Alfa AF: 0.539 Hom.: 56032

Bravo AF: 0.475

Asia WGS AF: 0.392 AC: 1356 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.025
DANN	Benign	0.74
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3789688; hg19: chr1-94691240;