rs12431381

chr14-59643053-T-C

Variant summary

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

The NM_021136.3(RTN1):c.1766-35561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,086 control chromosomes in the GnomAD database, including 11,224 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 0.35 (11224 hom., cov: 32)
• Consequence: RTN1 NM_021136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTN1	NM_021136.3	c.1766-35561A>G		intron_variant		ENST00000267484.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTN1	ENST00000267484.10	c.1766-35561A>G		intron_variant		1	NM_021136.3
RTN1	ENST00000432103.6	n.796-35561A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53168 AN: 151968 Hom.: 11222 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.350 AC: 53180 AN: 152086 Hom.: 11224 Cov.: 32 AF XY: 0.359 AC XY: 26654 AN XY: 74344

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.331

Alfa AF: 0.416 Hom.: 22366

Bravo AF: 0.325

Asia WGS AF: 0.359 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.3
Dann	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12431381; hg19: chr14-60109771;