14-59691018-C-T

Position:

• chr14-59691018-C-T

Variant summary

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

The ENST00000267484.10(RTN1):​c.1765+35901G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,880 control chromosomes in the GnomAD database, including 11,313 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 (11313 hom., cov: 31)
• Consequence: RTN1 ENST00000267484.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN1	NM_021136.3	c.1765+35901G>A		intron_variant		ENST00000267484.10	NP_066959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10	c.1765+35901G>A		intron_variant		1	NM_021136.3	ENSP00000267484
RTN1	ENST00000432103.6	n.795+35901G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53644 AN: 151760 Hom.: 11311 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.353 AC: 53644 AN: 151880 Hom.: 11313 Cov.: 31 AF XY: 0.360 AC XY: 26703 AN XY: 74224

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.330

Alfa AF: 0.421 Hom.: 12770

Bravo AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1952034; hg19: chr14-60157736;