Menu
GeneBe

6-106572119-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032730.5(RTN4IP1):c.1084-16C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,582,394 control chromosomes in the GnomAD database, including 12,959 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2461 hom., cov: 32)
Exomes 𝑓: 0.12 ( 10498 hom. )

Consequence

RTN4IP1
NM_032730.5 splice_polypyrimidine_tract, intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0970
Variant links:
Genes affected
RTN4IP1 (HGNC:18647): (reticulon 4 interacting protein 1) This gene encodes a mitochondrial protein that interacts with reticulon 4, which is a potent inhibitor of regeneration following spinal cord injury. This interaction may be important for reticulon-induced inhibition of neurite growth. Mutations in this gene can cause optic atrophy 10, with or without ataxia, cognitive disability, and seizures. There is a pseudogene for this gene on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-106572119-G-T is Benign according to our data. Variant chr6-106572119-G-T is described in ClinVar as [Benign]. Clinvar id is 1168415.Status of the report is criteria_provided_single_submitter, 1 stars.
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 = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RTN4IP1NM_032730.5 linkuse as main transcriptc.1084-16C>A splice_polypyrimidine_tract_variant, intron_variant ENST00000369063.8
RTN4IP1NM_001318746.1 linkuse as main transcriptc.784-16C>A splice_polypyrimidine_tract_variant, intron_variant
RTN4IP1XM_011536192.3 linkuse as main transcriptc.844-16C>A splice_polypyrimidine_tract_variant, intron_variant
RTN4IP1XM_017011376.3 linkuse as main transcriptc.*33-16C>A splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RTN4IP1ENST00000369063.8 linkuse as main transcriptc.1084-16C>A splice_polypyrimidine_tract_variant, intron_variant 1 NM_032730.5 P1Q8WWV3-1
RTN4IP1ENST00000539449.2 linkuse as main transcriptc.*33-16C>A splice_polypyrimidine_tract_variant, intron_variant 2
RTN4IP1ENST00000493619.1 linkuse as main transcriptn.82-16C>A splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 3
RTN4IP1ENST00000498091.1 linkuse as main transcriptn.305-16C>A splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.163
AC:
24726
AN:
152046
Hom.:
2459
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.282
Gnomad AMI
AF:
0.0877
Gnomad AMR
AF:
0.132
Gnomad ASJ
AF:
0.127
Gnomad EAS
AF:
0.142
Gnomad SAS
AF:
0.134
Gnomad FIN
AF:
0.123
Gnomad MID
AF:
0.184
Gnomad NFE
AF:
0.110
Gnomad OTH
AF:
0.164
GnomAD3 exomes
AF:
0.130
AC:
31876
AN:
245690
Hom.:
2301
AF XY:
0.128
AC XY:
17092
AN XY:
133064
show subpopulations
Gnomad AFR exome
AF:
0.287
Gnomad AMR exome
AF:
0.111
Gnomad ASJ exome
AF:
0.130
Gnomad EAS exome
AF:
0.131
Gnomad SAS exome
AF:
0.138
Gnomad FIN exome
AF:
0.116
Gnomad NFE exome
AF:
0.113
Gnomad OTH exome
AF:
0.132
GnomAD4 exome
AF:
0.117
AC:
167735
AN:
1430230
Hom.:
10498
Cov.:
25
AF XY:
0.117
AC XY:
83688
AN XY:
713168
show subpopulations
Gnomad4 AFR exome
AF:
0.287
Gnomad4 AMR exome
AF:
0.114
Gnomad4 ASJ exome
AF:
0.128
Gnomad4 EAS exome
AF:
0.144
Gnomad4 SAS exome
AF:
0.135
Gnomad4 FIN exome
AF:
0.112
Gnomad4 NFE exome
AF:
0.109
Gnomad4 OTH exome
AF:
0.128
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.163
AC:
24733
AN:
152164
Hom.:
2461
Cov.:
32
AF XY:
0.161
AC XY:
12006
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.281
Gnomad4 AMR
AF:
0.131
Gnomad4 ASJ
AF:
0.127
Gnomad4 EAS
AF:
0.142
Gnomad4 SAS
AF:
0.133
Gnomad4 FIN
AF:
0.123
Gnomad4 NFE
AF:
0.110
Gnomad4 OTH
AF:
0.163
Alfa
AF:
0.139
Hom.:
349
Bravo
AF:
0.169
Asia WGS
AF:
0.155
AC:
542
AN:
3478

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 testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
9.4
Dann
Benign
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs9486411; hg19: chr6-107019994; COSMIC: COSV64804912; COSMIC: COSV64804912; API