17-30971202-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_032322.4(RNF135):c.129C>T(p.His43His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,524,090 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0052 ( 12 hom., cov: 33)
Exomes 𝑓: 0.00046 ( 2 hom. )
Consequence
RNF135
NM_032322.4 synonymous
NM_032322.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.614
Publications
0 publications found
Genes affected
RNF135 (HGNC:21158): (ring finger protein 135) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. This gene is located in a chromosomal region known to be frequently deleted in patients with neurofibromatosis. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
RNF135 Gene-Disease associations (from GenCC):
- overgrowth-macrocephaly-facial dysmorphism syndromeInheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- overgrowth syndromeInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 17-30971202-C-T is Benign according to our data. Variant chr17-30971202-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 720084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.614 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00524 (798/152298) while in subpopulation AFR AF = 0.0185 (771/41572). AF 95% confidence interval is 0.0175. There are 12 homozygotes in GnomAd4. There are 370 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High AC in GnomAd4 at 798 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00522 AC: 795AN: 152190Hom.: 12 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
795
AN:
152190
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.000655 AC: 77AN: 117566 AF XY: 0.000477 show subpopulations
GnomAD2 exomes
AF:
AC:
77
AN:
117566
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000459 AC: 630AN: 1371792Hom.: 2 Cov.: 31 AF XY: 0.000390 AC XY: 264AN XY: 676668 show subpopulations
GnomAD4 exome
AF:
AC:
630
AN:
1371792
Hom.:
Cov.:
31
AF XY:
AC XY:
264
AN XY:
676668
show subpopulations
African (AFR)
AF:
AC:
486
AN:
29178
American (AMR)
AF:
AC:
45
AN:
35002
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24656
East Asian (EAS)
AF:
AC:
0
AN:
34404
South Asian (SAS)
AF:
AC:
2
AN:
78008
European-Finnish (FIN)
AF:
AC:
0
AN:
34300
Middle Eastern (MID)
AF:
AC:
3
AN:
4726
European-Non Finnish (NFE)
AF:
AC:
21
AN:
1074242
Other (OTH)
AF:
AC:
73
AN:
57276
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
41
82
122
163
204
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome AF: 0.00524 AC: 798AN: 152298Hom.: 12 Cov.: 33 AF XY: 0.00497 AC XY: 370AN XY: 74472 show subpopulations
GnomAD4 genome
AF:
AC:
798
AN:
152298
Hom.:
Cov.:
33
AF XY:
AC XY:
370
AN XY:
74472
show subpopulations
African (AFR)
AF:
AC:
771
AN:
41572
American (AMR)
AF:
AC:
22
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5184
South Asian (SAS)
AF:
AC:
0
AN:
4834
European-Finnish (FIN)
AF:
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67998
Other (OTH)
AF:
AC:
4
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
39
78
118
157
196
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Mar 23, 2021
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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