NM_004815.4:c.437+84A>G

Variant names:

• chr1-94209170-T-C
• rs2274788
• NM_004815.4:c.437+84A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004815.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP29	NM_004815.4	MANE Select	c.437+84A>G		intron	N/A	NP_004806.3
	ARHGAP29	NM_001328664.2		c.437+84A>G		intron	N/A	NP_001315593.1
	ARHGAP29	NM_001328666.2		c.437+84A>G		intron	N/A	NP_001315595.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARHGAP29	ENST00000260526.11	TSL:1 MANE Select	c.437+84A>G		intron	N/A	ENSP00000260526.6
	ARHGAP29	ENST00000370217.3	TSL:1	c.437+84A>G		intron	N/A	ENSP00000359237.3
	ARHGAP29	ENST00000552844.5	TSL:1	n.437+84A>G		intron	N/A	ENSP00000449764.1

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

African (AFR) AF: 0.0600 AC: 1226 AN: 20436

American (AMR) AF: 0.220 AC: 5703 AN: 25944

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 5554 AN: 20536

East Asian (EAS) AF: 0.296 AC: 10747 AN: 36318

South Asian (SAS) AF: 0.193 AC: 12513 AN: 64776

European-Finnish (FIN) AF: 0.203 AC: 9857 AN: 48550

Middle Eastern (MID) AF: 0.249 AC: 1106 AN: 4450

European-Non Finnish (NFE) AF: 0.258 AC: 157836 AN: 610870

Other (OTH) AF: 0.236 AC: 9567 AN: 40504

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

African (AFR) AF: 0.0658 AC: 2733 AN: 41532

American (AMR) AF: 0.237 AC: 3627 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3466

East Asian (EAS) AF: 0.325 AC: 1678 AN: 5170

South Asian (SAS) AF: 0.185 AC: 889 AN: 4816

European-Finnish (FIN) AF: 0.213 AC: 2258 AN: 10594

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17473 AN: 67984

Other (OTH) AF: 0.215 AC: 454 AN: 2112

Alfa AF: 0.236 Hom.: 12296

Bravo AF: 0.198

Asia WGS AF: 0.203 AC: 707 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.55
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2274788; hg19: chr1-94674726;