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GeneBe

1-94177640-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004815.4(ARHGAP29):c.2877G>A(p.Ala959=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000813 in 1,612,604 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 8 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 6 hom. )

Consequence

ARHGAP29
NM_004815.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.700
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-94177640-C-T is Benign according to our data. Variant chr1-94177640-C-T is described in ClinVar as [Benign]. Clinvar id is 718420.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.7 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARHGAP29NM_004815.4 linkuse as main transcriptc.2877G>A p.Ala959= synonymous_variant 22/23 ENST00000260526.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARHGAP29ENST00000260526.11 linkuse as main transcriptc.2877G>A p.Ala959= synonymous_variant 22/231 NM_004815.4 P1Q52LW3-1
ARHGAP29ENST00000482481.1 linkuse as main transcriptn.7453G>A non_coding_transcript_exon_variant 10/101
ARHGAP29ENST00000552844.5 linkuse as main transcriptc.2877G>A p.Ala959= synonymous_variant, NMD_transcript_variant 22/261

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00431
AC:
654
AN:
151870
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0154
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000788
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.00114
AC:
285
AN:
250298
Hom.:
1
AF XY:
0.000843
AC XY:
114
AN XY:
135240
show subpopulations
Gnomad AFR exome
AF:
0.0155
Gnomad AMR exome
AF:
0.000523
Gnomad ASJ exome
AF:
0.000597
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000661
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.000655
GnomAD4 exome
AF:
0.000448
AC:
654
AN:
1460616
Hom.:
6
Cov.:
31
AF XY:
0.000402
AC XY:
292
AN XY:
726514
show subpopulations
Gnomad4 AFR exome
AF:
0.0154
Gnomad4 AMR exome
AF:
0.000673
Gnomad4 ASJ exome
AF:
0.000460
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000582
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.00106
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00432
AC:
657
AN:
151988
Hom.:
8
Cov.:
32
AF XY:
0.00397
AC XY:
295
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.0154
Gnomad4 AMR
AF:
0.000787
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.00203
Hom.:
2
Bravo
AF:
0.00464
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
1.8
Dann
Benign
0.61

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.

Other links and lift over

dbSNP: rs79740616; hg19: chr1-94643196; COSMIC: COSV99557608; API