1-94238840-A-G

Variant names:

• chr1-94238840-A-G
• rs3814019
• ENST00000552844.5:n.-32-7197T>C

Variant summary

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

The ENST00000552844.5(ARHGAP29):​n.-32-7197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,102 control chromosomes in the GnomAD database, including 4,928 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 0.25 (4928 hom., cov: 32)
• Consequence: ARHGAP29 ENST00000552844.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957
• Publications: 2 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 Gene-Disease associations (from GenCC):

• cleft lip with or without cleft palate

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARHGAP29	NM_001328664.2	c.-32-7197T>C		intron_variant	Intron 1 of 22		NP_001315593.1
ARHGAP29	NM_001328665.2	c.13+8725T>C		intron_variant	Intron 1 of 21		NP_001315594.1
ARHGAP29	XM_011542439.3	c.-32-7197T>C		intron_variant	Intron 1 of 22		XP_011540741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARHGAP29	ENST00000552844.5	n.-32-7197T>C		intron_variant	Intron 1 of 25	1		ENSP00000449764.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38190 AN: 151984 Hom.: 4935 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.251 AC: 38186 AN: 152102 Hom.: 4928 Cov.: 32 AF XY: 0.248 AC XY: 18459 AN XY: 74368

African (AFR) AF: 0.256 AC: 10607 AN: 41490

American (AMR) AF: 0.228 AC: 3487 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2370 AN: 5168

South Asian (SAS) AF: 0.210 AC: 1014 AN: 4818

European-Finnish (FIN) AF: 0.224 AC: 2366 AN: 10568

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16619 AN: 67980

Other (OTH) AF: 0.256 AC: 542 AN: 2114

Alfa AF: 0.254 Hom.: 8360

Bravo AF: 0.255

Asia WGS AF: 0.294 AC: 1023 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.50
PhyloP100		0.96

Splicing

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

Other links and lift over

dbSNP: rs3814019; hg19: chr1-94704396;