rs3789688

Positions:

• chr1-94225684-T-C

Variant summary

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

The NM_004815.4(ARHGAP29):​c.206-5292A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,862 control chromosomes in the GnomAD database, including 18,099 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 0.48 (18099 hom., cov: 32)
• Consequence: ARHGAP29 NM_004815.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP29	NM_004815.4	c.206-5292A>G		intron_variant		ENST00000260526.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP29	ENST00000260526.11	c.206-5292A>G		intron_variant		1	NM_004815.4	P1
ARHGAP29	ENST00000370217.3	c.206-5292A>G		intron_variant		1
ARHGAP29	ENST00000552844.5	c.206-5292A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72516 AN: 151744 Hom.: 18107 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.477 AC: 72512 AN: 151862 Hom.: 18099 Cov.: 32 AF XY: 0.470 AC XY: 34883 AN XY: 74216

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.490

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.522

Alfa AF: 0.554 Hom.: 36866

Bravo AF: 0.475

Asia WGS AF: 0.392 AC: 1356 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.025
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3789688; hg19: chr1-94691240;