NM_021136.3:c.1765+53617A>C

Variant names:

• chr14-59673302-T-G
• rs17804446
• NM_021136.3:c.1765+53617A>C

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+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
• Publications: 5 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=-0.7).
• 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 rank	MANE	Protein	UniProt
RTN1	NM_021136.3	c.1765+53617A>C		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.1765+53617A>C		intron_variant	Intron 3 of 8	1	NM_021136.3	ENSP00000267484.5
RTN1	ENST00000432103.6	n.795+53617A>C		intron_variant	Intron 1 of 6	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

African (AFR) AF: 0.159 AC: 6589 AN: 41470

American (AMR) AF: 0.366 AC: 5589 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1400 AN: 3462

East Asian (EAS) AF: 0.466 AC: 2380 AN: 5106

South Asian (SAS) AF: 0.340 AC: 1633 AN: 4808

European-Finnish (FIN) AF: 0.579 AC: 6079 AN: 10502

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29565 AN: 67848

Other (OTH) AF: 0.342 AC: 721 AN: 2106

Alfa AF: 0.403 Hom.: 1934

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
PhyloP100		0.30
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: rs17804446; hg19: chr14-60140020;