1-94174310-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_004815.4(ARHGAP29):c.3345G>A(p.Gly1115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,614,076 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (3 hom.)
• Consequence: ARHGAP29 NM_004815.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.163

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 1-94174310-C-T is Benign according to our data. Variant chr1-94174310-C-T is described in ClinVar as [Benign]. Clinvar id is 775569.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.163 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP29	NM_004815.4	c.3345G>A	p.Gly1115=	synonymous_variant	23/23	ENST00000260526.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP29	ENST00000260526.11	c.3345G>A	p.Gly1115=	synonymous_variant	23/23	1	NM_004815.4	P1
ARHGAP29	ENST00000552844.5	c.3051+294G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 255 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00444

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000567

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.000477 AC: 120 AN: 251422 Hom.: 1 AF XY: 0.000412 AC XY: 56 AN XY: 135884

Gnomad AFR exome AF: 0.00406

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000369 AC: 539 AN: 1461890 Hom.: 3 Cov.: 35 AF XY: 0.000370 AC XY: 269 AN XY: 727246

Gnomad4 AFR exome AF: 0.00520

Gnomad4 AMR exome AF: 0.00116

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.000318

Gnomad4 NFE exome AF: 0.000218

Gnomad4 OTH exome AF: 0.000745

GnomAD4 genome AF: 0.00168 AC: 255 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.00144 AC XY: 107 AN XY: 74406

Gnomad4 AFR AF: 0.00443

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000567

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.000932 Hom.: 0

Bravo AF: 0.00213

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	1.0
Dann	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs74102117; hg19: chr1-94639866;