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GeneBe

6-106572005-A-G

Variant summary

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

The NM_032730.5(RTN4IP1):c.1182T>C(p.Asn394=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,609,902 control chromosomes in the GnomAD database, including 13,112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2478 hom., cov: 32)
Exomes 𝑓: 0.12 ( 10634 hom. )

Consequence

RTN4IP1
NM_032730.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0250
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]
CRYBG1 (HGNC:356): (crystallin beta-gamma domain containing 1) Predicted to enable carbohydrate binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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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=-0.84).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-106572005-A-G is Benign according to our data. Variant chr6-106572005-A-G is described in ClinVar as [Benign]. Clinvar id is 1168414.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=0.025 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 = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RTN4IP1NM_032730.5 linkuse as main transcriptc.1182T>C p.Asn394= synonymous_variant 9/9 ENST00000369063.8
CRYBG1NM_001371242.2 linkuse as main transcriptc.*3439A>G 3_prime_UTR_variant 22/22 ENST00000633556.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RTN4IP1ENST00000369063.8 linkuse as main transcriptc.1182T>C p.Asn394= synonymous_variant 9/91 NM_032730.5 P1Q8WWV3-1
CRYBG1ENST00000633556.3 linkuse as main transcriptc.*3439A>G 3_prime_UTR_variant 22/225 NM_001371242.2 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.163
AC:
24765
AN:
152026
Hom.:
2476
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:
0.124
Gnomad MID
AF:
0.187
Gnomad NFE
AF:
0.110
Gnomad OTH
AF:
0.164
GnomAD3 exomes
AF:
0.129
AC:
32160
AN:
249926
Hom.:
2323
AF XY:
0.127
AC XY:
17241
AN XY:
135332
show subpopulations
Gnomad AFR exome
AF:
0.287
Gnomad AMR exome
AF:
0.109
Gnomad ASJ exome
AF:
0.128
Gnomad EAS exome
AF:
0.130
Gnomad SAS exome
AF:
0.135
Gnomad FIN exome
AF:
0.117
Gnomad NFE exome
AF:
0.112
Gnomad OTH exome
AF:
0.132
GnomAD4 exome
AF:
0.116
AC:
169706
AN:
1457758
Hom.:
10634
Cov.:
28
AF XY:
0.117
AC XY:
84541
AN XY:
725478
show subpopulations
Gnomad4 AFR exome
AF:
0.285
Gnomad4 AMR exome
AF:
0.112
Gnomad4 ASJ exome
AF:
0.127
Gnomad4 EAS exome
AF:
0.144
Gnomad4 SAS exome
AF:
0.134
Gnomad4 FIN exome
AF:
0.113
Gnomad4 NFE exome
AF:
0.108
Gnomad4 OTH exome
AF:
0.127
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.163
AC:
24772
AN:
152144
Hom.:
2478
Cov.:
32
AF XY:
0.162
AC XY:
12024
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.281
Gnomad4 AMR
AF:
0.132
Gnomad4 ASJ
AF:
0.127
Gnomad4 EAS
AF:
0.142
Gnomad4 SAS
AF:
0.133
Gnomad4 FIN
AF:
0.124
Gnomad4 NFE
AF:
0.110
Gnomad4 OTH
AF:
0.163
Alfa
AF:
0.132
Hom.:
852
Bravo
AF:
0.169
Asia WGS
AF:
0.155
AC:
542
AN:
3478
EpiCase
AF:
0.117
EpiControl
AF:
0.128

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
-0.84
Cadd
Benign
0.66
Dann
Benign
0.54

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: rs9486410; hg19: chr6-107019880; COSMIC: COSV64806583; COSMIC: COSV64806583; API