rs146184061

Variant names:

• chr14-59607408-T-A
• rs146184061
• NM_021136.3:c.1850A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-59607408-T-A
• chr14-59607408-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021136.3(RTN1):​c.1850A>T​(p.Gln617Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000385 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00039 (0 hom.)
• Consequence: RTN1 NM_021136.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1233165).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN1	NM_021136.3	MANE Select	c.1850A>T	p.Gln617Leu	missense	Exon 4 of 9	NP_066959.1	Q16799-1
	RTN1	NM_206852.3		c.146A>T	p.Gln49Leu	missense	Exon 2 of 7	NP_996734.1	Q16799-3
	RTN1	NM_001363702.1		c.101A>T	p.Gln34Leu	missense	Exon 2 of 7	NP_001350631.1	A8MT72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN1	ENST00000267484.10	TSL:1 MANE Select	c.1850A>T	p.Gln617Leu	missense	Exon 4 of 9	ENSP00000267484.5	Q16799-1
	RTN1	ENST00000342503.8	TSL:1	c.146A>T	p.Gln49Leu	missense	Exon 2 of 7	ENSP00000340716.4	Q16799-3
	RTN1	ENST00000432103.6	TSL:1	n.880A>T		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152088 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000518 AC: 130 AN: 250786 AF XY: 0.000480

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000929

Gnomad NFE exome AF: 0.000917

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000393 AC: 574 AN: 1461702 Hom.: 0 Cov.: 32 AF XY: 0.000371 AC XY: 270 AN XY: 727122

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.000637 AC: 34 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000461 AC: 513 AN: 1111924

Other (OTH) AF: 0.000381 AC: 23 AN: 60394

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152206 Hom.: 0 Cov.: 31 AF XY: 0.000336 AC XY: 25 AN XY: 74390

African (AFR) AF: 0.000168 AC: 7 AN: 41544

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000428 Hom.: 0

Bravo AF: 0.000242

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000749 AC: 91

EpiCase AF: 0.000109

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	29
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.2
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.18
Sift	Benign	0.66	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.76
MVP		0.17
MPC		1.6
ClinPred		0.11	T
GERP RS		6.0
Varity_R		0.32
gMVP		0.79
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs146184061; hg19: chr14-60074126;