rs12431381

Variant names:

• chr14-59643053-T-C
• rs12431381
• NM_021136.3:c.1766-35561A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RTN1	NM_021136.3	c.1766-35561A>G		intron_variant	Intron 3 of 8	ENST00000267484.10	NP_066959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10	c.1766-35561A>G		intron_variant	Intron 3 of 8	1	NM_021136.3	ENSP00000267484.5
RTN1	ENST00000432103.6	n.796-35561A>G		intron_variant	Intron 1 of 6	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

African (AFR) AF: 0.106 AC: 4403 AN: 41502

American (AMR) AF: 0.364 AC: 5564 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1404 AN: 3468

East Asian (EAS) AF: 0.472 AC: 2432 AN: 5156

South Asian (SAS) AF: 0.349 AC: 1680 AN: 4816

European-Finnish (FIN) AF: 0.594 AC: 6279 AN: 10572

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30114 AN: 67974

Other (OTH) AF: 0.331 AC: 699 AN: 2110

Alfa AF: 0.406 Hom.: 50088

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
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12431381; hg19: chr14-60109771;