rs12750249

Variant names:

• chr1-94256104-T-C
• rs12750249
• ENST00000552844.5:n.-33+18908A>G

Variant summary

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

The ENST00000552844.5(ARHGAP29):​n.-33+18908A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,090 control chromosomes in the GnomAD database, including 4,061 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 0.21 (4061 hom., cov: 32)
• Consequence: ARHGAP29 ENST00000552844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843
• Publications: 7 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-AS1 (HGNC:54311): (ARHGAP29 antisense RNA 1)

ENSG00000236098 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000552844.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP29	ENST00000552844.5	TSL:1	n.-33+18908A>G		intron	N/A	ENSP00000449764.1
	ARHGAP29-AS1	ENST00000413103.4	TSL:5	n.489+5560T>C		intron	N/A
	ARHGAP29-AS1	ENST00000418242.3	TSL:5	n.421+6585T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31685 AN: 151972 Hom.: 4052 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.208 AC: 31708 AN: 152090 Hom.: 4061 Cov.: 32 AF XY: 0.211 AC XY: 15697 AN XY: 74322

African (AFR) AF: 0.0508 AC: 2109 AN: 41526

American (AMR) AF: 0.267 AC: 4074 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1570 AN: 5168

South Asian (SAS) AF: 0.165 AC: 796 AN: 4822

European-Finnish (FIN) AF: 0.287 AC: 3027 AN: 10542

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18678 AN: 67976

Other (OTH) AF: 0.207 AC: 437 AN: 2108

Alfa AF: 0.239 Hom.: 9399

Bravo AF: 0.201

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12750249; hg19: chr1-94721660;