Variant 6-106572005-A-G details in Genebe, Genetics Data Aggregator

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

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]

RTN4IP1 links:

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

CRYBG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

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

Synonymous conserved (PhyloP=0.025 with no splicing effect.

BA1

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
RTN4IP1	NM_032730.5 linkuse as main transcript	c.1182T>C	p.Asn394=	synonymous_variant	9/9	ENST00000369063.8
CRYBG1	NM_001371242.2 linkuse as main transcript	c.*3439A>G		3_prime_UTR_variant	22/22	ENST00000633556.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN4IP1	ENST00000369063.8 linkuse as main transcript	c.1182T>C	p.Asn394=	synonymous_variant	9/9	1	NM_032730.5	P1	Q8WWV3-1
CRYBG1	ENST00000633556.3 linkuse as main transcript	c.*3439A>G		3_prime_UTR_variant	22/22	5	NM_001371242.2	P1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24765

AN:

152026

Hom.:

2476

Cov.:

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.:

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

AF:

0.163

AC:

24772

AN:

152144

Hom.:

2478

Cov.:

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 submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over