rs12750249

Variant names:

• chr1-94256104-T-C
• rs12750249
• ENST00000552844.5:n.-33+18908A>G

Variant summary

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

The ENST00000552844.5(ARHGAP29):​n.-33+18908A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,090 control chromosomes in the GnomAD database, including 4,061 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 0.21 (4061 hom., cov: 32)
• Consequence: ARHGAP29 ENST00000552844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843
• Publications: 7 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-AS1 (HGNC:54311): (ARHGAP29 antisense RNA 1)

ENSG00000236098 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP29	XM_011542439.3	c.-33+18908A>G		intron_variant	Intron 1 of 22		XP_011540741.1
ARHGAP29	XM_047434754.1	c.-33+24220A>G		intron_variant	Intron 3 of 24		XP_047290710.1
ARHGAP29	XM_047434759.1	c.-33+24220A>G		intron_variant	Intron 2 of 23		XP_047290715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP29	ENST00000552844.5	n.-33+18908A>G		intron_variant	Intron 1 of 25	1		ENSP00000449764.1
ARHGAP29-AS1	ENST00000413103.4	n.489+5560T>C		intron_variant	Intron 3 of 4	5
ARHGAP29-AS1	ENST00000418242.3	n.421+6585T>C		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31685 AN: 151972 Hom.: 4052 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.208 AC: 31708 AN: 152090 Hom.: 4061 Cov.: 32 AF XY: 0.211 AC XY: 15697 AN XY: 74322

African (AFR) AF: 0.0508 AC: 2109 AN: 41526

American (AMR) AF: 0.267 AC: 4074 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3470

East Asian (EAS) AF: 0.304 AC: 1570 AN: 5168

South Asian (SAS) AF: 0.165 AC: 796 AN: 4822

European-Finnish (FIN) AF: 0.287 AC: 3027 AN: 10542

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18678 AN: 67976

Other (OTH) AF: 0.207 AC: 437 AN: 2108

Alfa AF: 0.239 Hom.: 9399

Bravo AF: 0.201

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.84

Splicing

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

Other links and lift over

dbSNP: rs12750249; hg19: chr1-94721660;