1-94238840-A-G

Position:

• chr1-94238840-A-G

Variant summary

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

The ENST00000552844.5(ARHGAP29):​c.-32-7197T>C variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.957

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=-0.83).
• 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/exons	MANE	Protein	UniProt
ARHGAP29	NM_001328664.2	c.-32-7197T>C		intron_variant			NP_001315593.1
ARHGAP29	NM_001328665.2	c.13+8725T>C		intron_variant			NP_001315594.1
ARHGAP29	XM_011542439.3	c.-32-7197T>C		intron_variant			XP_011540741.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARHGAP29	ENST00000552844.5	c.-32-7197T>C		intron_variant, NMD_transcript_variant		1		ENSP00000449764

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

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.256

Alfa AF: 0.256 Hom.: 4401

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3814019; hg19: chr1-94704396;