rs12750249

chr1-94256104-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000552844.5(ARHGAP29):c.-33+18908A>G variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843

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)

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP29-AS1	XR_001738153.3	n.540+5560T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP29-AS1	ENST00000656153.1	n.277+6585T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0508

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.207

Alfa AF: 0.256 Hom.: 7164

Bravo AF: 0.201

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	11
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12750249; hg19: chr1-94721660;