rs1576593

Positions:

• chr1-94166195-T-C

Variant summary

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

The variant allele was found at a frequency of 0.461 in 151,986 control chromosomes in the GnomAD database, including 16,654 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 0.46 (16654 hom., cov: 31)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.94166195T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP29	ENST00000552844.5	n.3051+8409A>G		intron_variant		1		ENSP00000449764.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69899 AN: 151868 Hom.: 16614 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.461 AC: 70006 AN: 151986 Hom.: 16654 Cov.: 31 AF XY: 0.465 AC XY: 34526 AN XY: 74266

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.380

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.426

Alfa AF: 0.444 Hom.: 1928

Bravo AF: 0.463

Asia WGS AF: 0.547 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.080
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1576593; hg19: chr1-94631751;