rs1541098

Positions:

• chr1-94202414-T-C

Variant summary

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

The ENST00000370217(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_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ARHGAP29	NM_004815.4	c.1143+130A>G		intron_variant		ENST00000260526.11	NP_004806.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP29	ENST00000370217	c.*91A>G		3_prime_UTR_variant	11/11	1		ENSP00000359237.3
ARHGAP29	ENST00000260526.11	c.1143+130A>G		intron_variant		1	NM_004815.4	ENSP00000260526.6
ARHGAP29	ENST00000552844.5	n.1143+130A>G		intron_variant		1		ENSP00000449764.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28330 AN: 152118 Hom.: 3221 Cov.: 33

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.: 12 AF XY: 0.232 AC XY: 110397 AN XY: 475186

Gnomad4 AFR exome AF: 0.0403

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.332

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.243

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.186 AC: 28357 AN: 152236 Hom.: 3230 Cov.: 33 AF XY: 0.189 AC XY: 14090 AN XY: 74436

Gnomad4 AFR AF: 0.0447

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.153

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.186

Alfa AF: 0.226 Hom.: 5959

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	11
DANN	Benign	0.21

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

LitVar

Other links and lift over

dbSNP: rs1541098; hg19: chr1-94667970;