6-106572213-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032730.5(RTN4IP1):c.1084-110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 869,464 control chromosomes in the GnomAD database, including 6,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1704 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4969 hom.)
• Consequence: RTN4IP1 NM_032730.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.50

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 6-106572213-A-G is Benign according to our data. Variant chr6-106572213-A-G is described in ClinVar as [Benign]. Clinvar id is 1278589.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTN4IP1	NM_032730.5	c.1084-110T>C		intron_variant		ENST00000369063.8
RTN4IP1	NM_001318746.1	c.784-110T>C		intron_variant
RTN4IP1	XM_011536192.3	c.844-110T>C		intron_variant
RTN4IP1	XM_017011376.3	c.*33-110T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN4IP1	ENST00000369063.8	c.1084-110T>C		intron_variant		1	NM_032730.5	P1
RTN4IP1	ENST00000539449.2	c.*33-110T>C		intron_variant		2
RTN4IP1	ENST00000493619.1	n.82-110T>C		intron_variant, non_coding_transcript_variant		3
RTN4IP1	ENST00000498091.1	n.305-110T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21416 AN: 151820 Hom.: 1702 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.114 AC: 82085 AN: 717522 Hom.: 4969 Cov.: 9 AF XY: 0.115 AC XY: 43527 AN XY: 377982

Gnomad4 AFR exome AF: 0.205

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.141 AC: 21420 AN: 151942 Hom.: 1704 Cov.: 32 AF XY: 0.141 AC XY: 10447 AN XY: 74272

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.154

Alfa AF: 0.0418 Hom.: 31

Bravo AF: 0.145

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.030
Dann	Benign	0.55

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

Other links and lift over

dbSNP: rs9486412; hg19: chr6-107020088;