Genetic Variant RICTOR:p.Leu1537Leu (chr5-38945513-C-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_152756.5(RICTOR):c.4611G>T(p.Leu1537Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,612,966 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

RICTOR
NM_152756.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.113

Publications

0 publications found

Variant links:

Genes affected

RICTOR (HGNC:28611): (RPTOR independent companion of MTOR complex 2) RICTOR and MTOR (FRAP1; MIM 601231) are components of a protein complex that integrates nutrient- and growth factor-derived signals to regulate cell growth (Sarbassov et al., 2004 [PubMed 15268862]).[supplied by OMIM, Mar 2008]

RICTOR links:

OSMR (HGNC:8507): (oncostatin M receptor) This gene encodes a member of the type I cytokine receptor family. The encoded protein heterodimerizes with interleukin 6 signal transducer to form the type II oncostatin M receptor and with interleukin 31 receptor A to form the interleukin 31 receptor, and thus transduces oncostatin M and interleukin 31 induced signaling events. Mutations in this gene have been associated with familial primary localized cutaneous amyloidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

OSMR Gene-Disease associations (from GenCC):

amyloidosis, primary localized cutaneous, 1
Inheritance: AD, SD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial primary localized cutaneous amyloidosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

OSMR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 5-38945513-C-A is Benign according to our data. Variant chr5-38945513-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3025361.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.113 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152756.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RICTOR	NM_152756.5	MANE Select	c.4611G>T	p.Leu1537Leu	synonymous	Exon 34 of 38	NP_689969.2
RICTOR	NM_001285439.2		c.4683G>T	p.Leu1561Leu	synonymous	Exon 35 of 39	NP_001272368.1	Q6R327-3
RICTOR	NM_001438246.1		c.4635G>T	p.Leu1545Leu	synonymous	Exon 34 of 38	NP_001425175.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RICTOR	ENST00000357387.8	TSL:1 MANE Select	c.4611G>T	p.Leu1537Leu	synonymous	Exon 34 of 38	ENSP00000349959.3	Q6R327-1
RICTOR	ENST00000296782.10	TSL:1	c.4683G>T	p.Leu1561Leu	synonymous	Exon 35 of 39	ENSP00000296782.5	Q6R327-3
RICTOR	ENST00000511516.5	TSL:1	n.*3721G>T		non_coding_transcript_exon	Exon 34 of 38	ENSP00000423019.1	Q6R327-4

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000734

AC:

184

AN:

250826

AF XY:

0.000664

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000359

AC:

524

AN:

1460764

Hom.:

Cov.:

AF XY:

0.000371

AC XY:

270

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33458

American (AMR)

AF:

0.000358

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

367

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000594

AC:

AN:

1111048

Other (OTH)

AF:

0.00121

AC:

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000375

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00101

Hom.:

Bravo

AF:

0.000317

EpiCase

AF:

0.000709

EpiControl

AF:

0.000297

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

4.6

(source)

DANN

Benign

0.73

PhyloP100

-0.11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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