rs1576593

Variant names:

• chr1-94166195-T-C
• rs1576593
• ENST00000552844.5:n.3051+8409A>G

Variant summary

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

The ENST00000552844.5(ARHGAP29):​n.3051+8409A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: ARHGAP29 ENST00000552844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 4 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=-0.97).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP29	ENST00000552844.5	n.3051+8409A>G		intron_variant	Intron 23 of 25	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

African (AFR) AF: 0.562 AC: 23298 AN: 41448

American (AMR) AF: 0.458 AC: 6990 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1319 AN: 3468

East Asian (EAS) AF: 0.561 AC: 2892 AN: 5152

South Asian (SAS) AF: 0.485 AC: 2333 AN: 4808

European-Finnish (FIN) AF: 0.457 AC: 4828 AN: 10560

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27119 AN: 67968

Other (OTH) AF: 0.426 AC: 898 AN: 2110

Alfa AF: 0.448 Hom.: 2050

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
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs1576593; hg19: chr1-94631751;