14-59691018-C-T

Variant names:

• chr14-59691018-C-T
• rs1952034
• NM_021136.3:c.1765+35901G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021136.3(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 NM_021136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021136.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN1	NM_021136.3	MANE Select	c.1765+35901G>A		intron	N/A	NP_066959.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN1	ENST00000267484.10	TSL:1 MANE Select	c.1765+35901G>A		intron	N/A	ENSP00000267484.5
	RTN1	ENST00000432103.6	TSL:1	n.795+35901G>A		intron	N/A
	RTN1	ENST00000966440.1		c.1765+35901G>A		intron	N/A	ENSP00000636499.1

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

African (AFR) AF: 0.109 AC: 4535 AN: 41442

American (AMR) AF: 0.380 AC: 5793 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2148 AN: 5152

South Asian (SAS) AF: 0.389 AC: 1874 AN: 4818

European-Finnish (FIN) AF: 0.550 AC: 5794 AN: 10534

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30990 AN: 67892

Other (OTH) AF: 0.330 AC: 696 AN: 2110

Alfa AF: 0.410 Hom.: 35386

Bravo AF: 0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.31
PhyloP100		0.28
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: rs1952034; hg19: chr14-60157736;