Genetic Variant RTN1:c.2113-639A>C (chr14-59604560-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021136.3(RTN1):c.2113-639A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,180 control chromosomes in the GnomAD database, including 8,012 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 0.32 ( 7992 hom., cov: 32)

Exomes 𝑓: 0.51 ( 20 hom. )

Consequence

RTN1
NM_021136.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Publications

3 publications found

Variant links:

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]

RTN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RTN1	NM_021136.3	MANE Select	c.2113-639A>C	intron	N/A	NP_066959.1
RTN1	NM_206852.3		c.409-639A>C	intron	N/A	NP_996734.1
RTN1	NM_001363702.1		c.364-639A>C	intron	N/A	NP_001350631.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RTN1	ENST00000267484.10	TSL:1 MANE Select	c.2113-639A>C	intron	N/A	ENSP00000267484.5
RTN1	ENST00000342503.8	TSL:1	c.409-639A>C	intron	N/A	ENSP00000340716.4
RTN1	ENST00000432103.6	TSL:1	n.1143-639A>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48655

AN:

151922

Hom.:

7994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.417

Gnomad NFE

AF:

0.319

Gnomad OTH

AF:

0.339

GnomAD4 exome

AF:

0.507

AC:

AN:

138

Hom.:

Cov.:

AF XY:

0.443

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.800

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.833

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.451

AC:

AN:

102

Other (OTH)

AF:

0.800

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.320

AC:

48676

AN:

152042

Hom.:

7992

Cov.:

AF XY:

0.319

AC XY:

23692

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.329

AC:

13626

AN:

41460

American (AMR)

AF:

0.363

AC:

5551

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

1212

AN:

3472

East Asian (EAS)

AF:

0.150

AC:

777

AN:

5170

South Asian (SAS)

AF:

0.411

AC:

1977

AN:

4816

European-Finnish (FIN)

AF:

0.264

AC:

2788

AN:

10568

Middle Eastern (MID)

AF:

0.428

AC:

125

AN:

292

European-Non Finnish (NFE)

AF:

0.319

AC:

21671

AN:

67964

Other (OTH)

AF:

0.334

AC:

707

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1745

3491

5236

6982

8727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.316

Hom.:

1352

Bravo

AF:

0.326

Asia WGS

AF:

0.287

AC:

996

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.6

(source)

DANN

Benign

0.49

PhyloP100

-0.087

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over