rs3789689

Positions:

• chr1-94220029-T-G

Variant summary

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

The NM_004815.4(ARHGAP29):​c.340+229A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,246 control chromosomes in the GnomAD database, including 1,247 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 0.11 (1247 hom., cov: 32)
• Consequence: ARHGAP29 NM_004815.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.201

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP29	NM_004815.4	c.340+229A>C		intron_variant		ENST00000260526.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP29	ENST00000260526.11	c.340+229A>C		intron_variant		1	NM_004815.4	P1
ARHGAP29	ENST00000370217.3	c.340+229A>C		intron_variant		1
ARHGAP29	ENST00000552844.5	c.340+229A>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17184 AN: 152128 Hom.: 1241 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.0618

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0718

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.113 AC: 17206 AN: 152246 Hom.: 1247 Cov.: 32 AF XY: 0.111 AC XY: 8281 AN XY: 74426

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.0619

Gnomad4 FIN AF: 0.0761

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.0931

Alfa AF: 0.0799 Hom.: 671

Bravo AF: 0.119

Asia WGS AF: 0.122 AC: 422 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.57

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: rs3789689; hg19: chr1-94685585;