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GeneBe

8-42870035-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_030954.4(RNF170):c.291G>A(p.Pro97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,614,048 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 88 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 70 hom. )

Consequence

RNF170
NM_030954.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.267
Variant links:
Genes affected
RNF170 (HGNC:25358): (ring finger protein 170) This gene encodes a RING domain-containing protein that resides in the endoplasmic reticulum (ER) membrane. This protein functions as an E3 ubiquitin ligase and mediates ubiquitination and processing of inositol 1,4,5-trisphosphate (IP3) receptors via the ER-associated protein degradation pathway. It is recruited to the activated IP3 receptors by the ERLIN1/ERLIN2 complex to which it is constitutively bound. Mutations in this gene are associated with autosomal dominant sensory ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-42870035-C-T is Benign according to our data. Variant chr8-42870035-C-T is described in ClinVar as [Benign]. Clinvar id is 768237.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-42870035-C-T is described in Lovd as [Benign].
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=-0.267 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF170NM_030954.4 linkuse as main transcriptc.291G>A p.Pro97= synonymous_variant 4/7 ENST00000527424.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF170ENST00000527424.6 linkuse as main transcriptc.291G>A p.Pro97= synonymous_variant 4/71 NM_030954.4 P1Q96K19-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0181
AC:
2746
AN:
152120
Hom.:
88
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0641
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00400
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00909
GnomAD3 exomes
AF:
0.00470
AC:
1180
AN:
251300
Hom.:
37
AF XY:
0.00353
AC XY:
479
AN XY:
135800
show subpopulations
Gnomad AFR exome
AF:
0.0667
Gnomad AMR exome
AF:
0.00191
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000792
Gnomad OTH exome
AF:
0.00261
GnomAD4 exome
AF:
0.00179
AC:
2620
AN:
1461810
Hom.:
70
Cov.:
31
AF XY:
0.00151
AC XY:
1100
AN XY:
727208
show subpopulations
Gnomad4 AFR exome
AF:
0.0660
Gnomad4 AMR exome
AF:
0.00241
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000540
Gnomad4 OTH exome
AF:
0.00364
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0181
AC:
2748
AN:
152238
Hom.:
88
Cov.:
32
AF XY:
0.0180
AC XY:
1339
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0640
Gnomad4 AMR
AF:
0.00399
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00900
Alfa
AF:
0.00486
Hom.:
24
Bravo
AF:
0.0197
Asia WGS
AF:
0.00202
AC:
8
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

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
-0.81
Cadd
Benign
6.5
Dann
Benign
0.78
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs11989986; hg19: chr8-42725178; API