1-94177604-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_004815.4(ARHGAP29):c.2905+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,584,400 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (7 hom.)
• Consequence: ARHGAP29 NM_004815.4 splice_region, intron
• Scores: Splicing: ADA: 0.0008013
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.335

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=-0.67).
• BP6: Variant 1-94177604-C-T is Benign according to our data. Variant chr1-94177604-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 780083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-94177604-C-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP29	NM_004815.4	c.2905+8G>A		splice_region_variant, intron_variant		ENST00000260526.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP29	ENST00000260526.11	c.2905+8G>A		splice_region_variant, intron_variant		1	NM_004815.4	P1
ARHGAP29	ENST00000482481.1	n.7489G>A		non_coding_transcript_exon_variant	10/10	1
ARHGAP29	ENST00000552844.5	c.2905+8G>A		splice_region_variant, intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00209 AC: 318 AN: 151820 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000605

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000856

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00200 AC: 469 AN: 234752 Hom.: 1 AF XY: 0.00195 AC XY: 247 AN XY: 126870

Gnomad AFR exome AF: 0.000379

Gnomad AMR exome AF: 0.000130

Gnomad ASJ exome AF: 0.00172

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000943

Gnomad NFE exome AF: 0.00380

Gnomad OTH exome AF: 0.00176

GnomAD4 exome AF: 0.00275 AC: 3938 AN: 1432462 Hom.: 7 Cov.: 30 AF XY: 0.00269 AC XY: 1916 AN XY: 711758

Gnomad4 AFR exome AF: 0.000313

Gnomad4 AMR exome AF: 0.000199

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00125

Gnomad4 NFE exome AF: 0.00340

Gnomad4 OTH exome AF: 0.00145

GnomAD4 genome AF: 0.00209 AC: 318 AN: 151938 Hom.: 0 Cov.: 32 AF XY: 0.00209 AC XY: 155 AN XY: 74242

Gnomad4 AFR AF: 0.000603

Gnomad4 AMR AF: 0.000459

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000856

Gnomad4 NFE AF: 0.00391

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00285 Hom.: 0

Bravo AF: 0.00187

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	ARHGAP29: BP4 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	9.3
Dann	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00080
dbscSNV1_RF	Benign	0.0020
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: rs146090842; hg19: chr1-94643160;