rs10483717

chr14-59604560-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021136.3(RTN1):c.2113-639A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,180 control chromosomes in the GnomAD database, including 8,012 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (7992 hom., cov: 32)
  • Exomes 𝑓: 0.51 (20 hom.)
• Consequence: RTN1 NM_021136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

Genes affected

RTN1 (HGNC:10467): (reticulon 1) This gene belongs to the family of reticulon encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. This gene is considered to be a specific marker for neurological diseases and cancer, and is a potential molecular target for therapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTN1	NM_021136.3	c.2113-639A>C		intron_variant		ENST00000267484.10
RTN1	NM_001363702.1	c.364-639A>C		intron_variant
RTN1	NM_206852.3	c.409-639A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN1	ENST00000267484.10	c.2113-639A>C		intron_variant		1	NM_021136.3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48655 AN: 151922 Hom.: 7994 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.339

GnomAD4 exome AF: 0.507 AC: 70 AN: 138 Hom.: 20 Cov.: 0 AF XY: 0.443 AC XY: 31 AN XY: 70

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.800

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.451

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.320 AC: 48676 AN: 152042 Hom.: 7992 Cov.: 32 AF XY: 0.319 AC XY: 23692 AN XY: 74320

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.334

Alfa AF: 0.317 Hom.: 1309

Bravo AF: 0.326

Asia WGS AF: 0.287 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.6
Dann	Benign	0.49

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: rs10483717; hg19: chr14-60071278;