1-94220029-T-G

Variant names:

• chr1-94220029-T-G
• rs3789689
• NM_004815.4:c.340+229A>C

Variant summary

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

The NM_004815.4(ARHGAP29):​c.340+229A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,246 control chromosomes in the GnomAD database, including 1,247 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 0.11 (1247 hom., cov: 32)
• Consequence: ARHGAP29 NM_004815.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004815.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP29	NM_004815.4	MANE Select	c.340+229A>C		intron	N/A	NP_004806.3
	ARHGAP29	NM_001328664.2		c.340+229A>C		intron	N/A	NP_001315593.1
	ARHGAP29	NM_001328666.2		c.340+229A>C		intron	N/A	NP_001315595.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP29	ENST00000260526.11	TSL:1 MANE Select	c.340+229A>C		intron	N/A	ENSP00000260526.6
	ARHGAP29	ENST00000370217.3	TSL:1	c.340+229A>C		intron	N/A	ENSP00000359237.3
	ARHGAP29	ENST00000552844.5	TSL:1	n.340+229A>C		intron	N/A	ENSP00000449764.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17184 AN: 152128 Hom.: 1241 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0718

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.113 AC: 17206 AN: 152246 Hom.: 1247 Cov.: 32 AF XY: 0.111 AC XY: 8281 AN XY: 74426

African (AFR) AF: 0.197 AC: 8173 AN: 41524

American (AMR) AF: 0.108 AC: 1651 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 303 AN: 3470

East Asian (EAS) AF: 0.154 AC: 795 AN: 5172

South Asian (SAS) AF: 0.0619 AC: 299 AN: 4832

European-Finnish (FIN) AF: 0.0761 AC: 808 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0719 AC: 4888 AN: 68018

Other (OTH) AF: 0.0931 AC: 197 AN: 2116

Alfa AF: 0.0887 Hom.: 2353

Bravo AF: 0.119

Asia WGS AF: 0.122 AC: 422 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.57
PhyloP100		0.20
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: rs3789689; hg19: chr1-94685585;