NM_032730.5:c.1182T>C

Variant names:

• chr6-106572005-A-G
• rs9486410
• NM_032730.5:c.1182T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_032730.5(RTN4IP1):​c.1182T>C​(p.Asn394Asn) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0250
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032730.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4IP1	NM_032730.5	MANE Select	c.1182T>C	p.Asn394Asn	synonymous	Exon 9 of 9	NP_116119.2	Q8WWV3-1
	CRYBG1	NM_001371242.2	MANE Select	c.*3439A>G		3_prime_UTR	Exon 22 of 22	NP_001358171.1	Q9Y4K1-3
	RTN4IP1	NM_001318746.1		c.882T>C	p.Asn294Asn	synonymous	Exon 9 of 9	NP_001305675.1	Q8WWV3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN4IP1	ENST00000369063.8	TSL:1 MANE Select	c.1182T>C	p.Asn394Asn	synonymous	Exon 9 of 9	ENSP00000358059.3	Q8WWV3-1
	CRYBG1	ENST00000633556.3	TSL:5 MANE Select	c.*3439A>G		3_prime_UTR	Exon 22 of 22	ENSP00000488010.2	Q9Y4K1-3
	RTN4IP1	ENST00000539449.2	TSL:2	c.*131T>C		splice_region	Exon 6 of 6	ENSP00000444261.1	G3V1R2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24765 AN: 152026 Hom.: 2476 Cov.: 32

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

GnomAD2 exomes AF: 0.129 AC: 32160 AN: 249926 AF XY: 0.127

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 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

African (AFR) AF: 0.285 AC: 9507 AN: 33338

American (AMR) AF: 0.112 AC: 5009 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3312 AN: 26108

East Asian (EAS) AF: 0.144 AC: 5713 AN: 39676

South Asian (SAS) AF: 0.134 AC: 11543 AN: 86114

European-Finnish (FIN) AF: 0.113 AC: 6014 AN: 53232

Middle Eastern (MID) AF: 0.191 AC: 1102 AN: 5758

European-Non Finnish (NFE) AF: 0.108 AC: 119862 AN: 1108620

Other (OTH) AF: 0.127 AC: 7644 AN: 60220

GnomAD4 genome AF: 0.163 AC: 24772 AN: 152144 Hom.: 2478 Cov.: 32 AF XY: 0.162 AC XY: 12024 AN XY: 74382

African (AFR) AF: 0.281 AC: 11661 AN: 41448

American (AMR) AF: 0.132 AC: 2011 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 440 AN: 3468

East Asian (EAS) AF: 0.142 AC: 736 AN: 5188

South Asian (SAS) AF: 0.133 AC: 641 AN: 4816

European-Finnish (FIN) AF: 0.124 AC: 1315 AN: 10596

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7490 AN: 68016

Other (OTH) AF: 0.163 AC: 345 AN: 2116

Alfa AF: 0.133 Hom.: 869

Bravo AF: 0.169

Asia WGS AF: 0.155 AC: 542 AN: 3478

EpiCase AF: 0.117

EpiControl AF: 0.128

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.66
DANN	Benign	0.54
PhyloP100		0.025
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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