rs1048854

Positions:

• chr1-94177975-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000260526.11(ARHGAP29):​c.2673A>G​(p.Gln891=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,613,954 control chromosomes in the GnomAD database, including 51,897 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 (3793 hom., cov: 32)
  • Exomes 𝑓: 0.25 (48104 hom.)
• Consequence: ARHGAP29 ENST00000260526.11 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=0.397 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGAP29	NM_004815.4	c.2673A>G	p.Gln891=	synonymous_variant	21/23	ENST00000260526.11	NP_004806.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP29	ENST00000260526.11	c.2673A>G	p.Gln891=	synonymous_variant	21/23	1	NM_004815.4	ENSP00000260526	P1
ARHGAP29	ENST00000482481.1	n.7249A>G		non_coding_transcript_exon_variant	9/10	1
ARHGAP29	ENST00000552844.5	c.2673A>G	p.Gln891=	synonymous_variant, NMD_transcript_variant	21/26	1		ENSP00000449764

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29960 AN: 152030 Hom.: 3795 Cov.: 32

Gnomad AFR AF: 0.0662

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.235

GnomAD3 exomes AF: 0.219 AC: 55103 AN: 251332 Hom.: 7008 AF XY: 0.225 AC XY: 30580 AN XY: 135840

Gnomad AFR exome AF: 0.0593

Gnomad AMR exome AF: 0.213

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.00266

Gnomad SAS exome AF: 0.194

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.249 AC: 364483 AN: 1461806 Hom.: 48104 Cov.: 35 AF XY: 0.249 AC XY: 181424 AN XY: 727206

Gnomad4 AFR exome AF: 0.0596

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.00194

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.197 AC: 29958 AN: 152148 Hom.: 3793 Cov.: 32 AF XY: 0.193 AC XY: 14387 AN XY: 74372

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.232

Alfa AF: 0.255 Hom.: 12769

Bravo AF: 0.190

Asia WGS AF: 0.0920 AC: 322 AN: 3478

EpiCase AF: 0.278

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.47

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: rs1048854; hg19: chr1-94643531; COSMIC: COSV53108307;