chr14-59746490-C-G

Variant names:

• chr14-59746490-C-G
• rs112705146
• NM_021136.3:c.242-9G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_021136.3(RTN1):​c.242-9G>C variant causes a 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 intron
• Scores: Splicing: ADA: 0.00003851
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.24

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=-0.44).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN1	NM_021136.3	c.242-9G>C		intron_variant	Intron 1 of 8	ENST00000267484.10	NP_066959.1
RTN1	XM_011537063.4	c.242-9G>C		intron_variant	Intron 1 of 3		XP_011535365.1
RTN1	XM_047431674.1	c.242-9G>C		intron_variant	Intron 1 of 3		XP_047287630.1
RTN1	XR_007064042.1	n.388-9G>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10	c.242-9G>C		intron_variant	Intron 1 of 8	1	NM_021136.3	ENSP00000267484.5

Frequencies

GnomAD3 genomes AF: 0.00657 AC: 1000 AN: 152160 Hom.: 14 Cov.: 32

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

GnomAD2 exomes AF: 0.00201 AC: 406 AN: 202010 AF XY: 0.00144

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 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.: 10 Cov.: 32 AF XY: 0.000577 AC XY: 403 AN XY: 698580

Gnomad4 AFR exome AF: 0.0228 AC: 736 AN: 32324

Gnomad4 AMR exome AF: 0.00120 AC: 48 AN: 39994

Gnomad4 ASJ exome AF: 0.000132 AC: 3 AN: 22644

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39470

Gnomad4 SAS exome AF: 0.000143 AC: 11 AN: 76916

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 47280

Gnomad4 NFE exome AF: 0.0000211 AC: 23 AN: 1090850

Gnomad4 Remaining exome AF: 0.00159 AC: 93 AN: 58512

GnomAD4 genome AF: 0.00659 AC: 1003 AN: 152278 Hom.: 14 Cov.: 32 AF XY: 0.00611 AC XY: 455 AN XY: 74476

Gnomad4 AFR AF: 0.0234 AC: 0.0233912 AN: 0.0233912

Gnomad4 AMR AF: 0.000981 AC: 0.000980905 AN: 0.000980905

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000414 AC: 0.000414422 AN: 0.000414422

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000588 AC: 0.0000588097 AN: 0.0000588097

Gnomad4 OTH AF: 0.00425 AC: 0.00425331 AN: 0.00425331

Alfa AF: 0.00385 Hom.: 1

Bravo AF: 0.00747

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 23, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.53
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs112705146; hg19: chr14-60213208;