rs17804446

Positions:

• chr14-59673302-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.1765+53617A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 151,770 control chromosomes in the GnomAD database, including 11,112 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 0.36 (11112 hom., cov: 31)
• Consequence: RTN1 NM_021136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302

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=-0.7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTN1	NM_021136.3	c.1765+53617A>C		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+53617A>C		intron_variant		1	NM_021136.3	ENSP00000267484
RTN1	ENST00000432103.6	n.795+53617A>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54522 AN: 151654 Hom.: 11112 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.359 AC: 54540 AN: 151770 Hom.: 11112 Cov.: 31 AF XY: 0.367 AC XY: 27222 AN XY: 74134

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.366

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.342

Alfa AF: 0.413 Hom.: 1925

Bravo AF: 0.337

Asia WGS AF: 0.361 AC: 1262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.7
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17804446; hg19: chr14-60140020;