1-94209170-T-C

Position:

• chr1-94209170-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.437+84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,024,554 control chromosomes in the GnomAD database, including 31,147 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 0.20 (3595 hom., cov: 32)
  • Exomes 𝑓: 0.25 (27552 hom.)
• Consequence: ARHGAP29 NM_004815.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.296

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP29	NM_004815.4	c.437+84A>G		intron_variant		ENST00000260526.11	NP_004806.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP29	ENST00000260526.11	c.437+84A>G		intron_variant		1	NM_004815.4	ENSP00000260526	P1
ARHGAP29	ENST00000370217.3	c.437+84A>G		intron_variant		1		ENSP00000359237
ARHGAP29	ENST00000552844.5	c.437+84A>G		intron_variant, NMD_transcript_variant		1		ENSP00000449764

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30307 AN: 152052 Hom.: 3599 Cov.: 32

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.245 AC: 214109 AN: 872384 Hom.: 27552 AF XY: 0.245 AC XY: 110923 AN XY: 452820

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.270

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.199 AC: 30291 AN: 152170 Hom.: 3595 Cov.: 32 AF XY: 0.199 AC XY: 14773 AN XY: 74400

Gnomad4 AFR AF: 0.0658

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.215

Alfa AF: 0.250 Hom.: 7622

Bravo AF: 0.198

Asia WGS AF: 0.203 AC: 707 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.55

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: rs2274788; hg19: chr1-94674726;