Variant chr14-59746490-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_021136.3(RTN1):c.242-9G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,565,768 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 10 hom. )

Consequence

RTN1
NM_021136.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003851

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.24

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 14-59746490-C-G is Benign according to our data. Variant chr14-59746490-C-G is described in ClinVar as [Benign]. Clinvar id is 790143.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00659 (1003/152278) while in subpopulation AFR AF= 0.0234 (972/41554). AF 95% confidence interval is 0.0222. There are 14 homozygotes in gnomad4. There are 455 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
RTN1	NM_021136.3 linkuse as main transcript	c.242-9G>C	splice_polypyrimidine_tract_variant, intron_variant	ENST00000267484.10	NP_066959.1
RTN1	XM_011537063.4 linkuse as main transcript	c.242-9G>C	splice_polypyrimidine_tract_variant, intron_variant		XP_011535365.1
RTN1	XM_047431674.1 linkuse as main transcript	c.242-9G>C	splice_polypyrimidine_tract_variant, intron_variant		XP_047287630.1
RTN1	XR_007064042.1 linkuse as main transcript	n.388-9G>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10 linkuse as main transcript	c.242-9G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_021136.3	ENSP00000267484		Q16799-1

Frequencies

GnomAD3 genomes

AF:

0.00657

AC:

1000

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00201

AC:

406

AN:

202010

Hom.:

AF XY:

0.00144

AC XY:

155

AN XY:

107712

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.000341

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000148

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000648

Gnomad OTH exome

AF:

0.00101

GnomAD4 exome

AF:

0.000652

AC:

921

AN:

1413490

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

403

AN XY:

698580

show subpopulations

Gnomad4 AFR exome

AF:

0.0228

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.000132

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000211

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00659

AC:

1003

AN:

152278

Hom.:

Cov.:

AF XY:

0.00611

AC XY:

455

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0234

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00385

Hom.:

Bravo

AF:

0.00747

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000039

dbscSNV1_RF

Benign

0.064

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over