Variant 1-94177673-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004815.4(ARHGAP29):c.2844A>C(p.Thr948=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,702 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

ARHGAP29
NM_004815.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.421

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-94177673-T-G is Benign according to our data. Variant chr1-94177673-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3045862.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-94177673-T-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP29	NM_004815.4 linkuse as main transcript	c.2844A>C	p.Thr948=	synonymous_variant	22/23	ENST00000260526.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP29	ENST00000260526.11 linkuse as main transcript	c.2844A>C	p.Thr948=	synonymous_variant	22/23	1	NM_004815.4	P1	Q52LW3-1
ARHGAP29	ENST00000482481.1 linkuse as main transcript	n.7420A>C		non_coding_transcript_exon_variant	10/10	1
ARHGAP29	ENST00000552844.5 linkuse as main transcript	c.2844A>C	p.Thr948=	synonymous_variant, NMD_transcript_variant	22/26	1

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000793

AC:

199

AN:

250966

Hom.:

AF XY:

0.000789

AC XY:

107

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000952

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.00105

AC:

1540

AN:

1461444

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

753

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00276

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152258

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000965

Hom.:

Bravo

AF:

0.000680

EpiCase

AF:

0.000873

EpiControl

AF:

0.00125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ARHGAP29-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

7.9

Dann

Benign

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over