Genetic Variant NM_003999.3:c.1090T>C (chr5-38903980-T-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003999.3(OSMR):c.1090T>C(p.Tyr364His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,040 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 7 hom., cov: 33)

Exomes 𝑓: 0.013 ( 143 hom. )

Consequence

OSMR
NM_003999.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0290

Variant links:

Genes affected

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01022765).

BP6

Variant 5-38903980-T-C is Benign according to our data. Variant chr5-38903980-T-C is described in ClinVar as [Benign]. Clinvar id is 791577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSMR	NM_003999.3 link	c.1090T>C	p.Tyr364His	missense_variant	Exon 8 of 18	ENST00000274276.8	NP_003990.1	Q99650-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSMR	ENST00000274276.8 link	c.1090T>C	p.Tyr364His	missense_variant	Exon 8 of 18	1	NM_003999.3	ENSP00000274276.3		Q99650-1

Frequencies

GnomAD3 genomes

AF:

0.00850

AC:

1293

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00868

AC:

2180

AN:

251192

Hom.:

AF XY:

0.00877

AC XY:

1191

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00203

Gnomad FIN exome

AF:

0.0168

Gnomad NFE exome

AF:

0.0135

Gnomad OTH exome

AF:

0.00801

GnomAD4 exome

AF:

0.0126

AC:

18358

AN:

1461734

Hom.:

143

Cov.:

AF XY:

0.0121

AC XY:

8828

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00226

Gnomad4 FIN exome

AF:

0.0174

Gnomad4 NFE exome

AF:

0.0147

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00849

AC:

1293

AN:

152306

Hom.:

Cov.:

AF XY:

0.00838

AC XY:

624

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00262

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.0119

Hom.:

Bravo

AF:

0.00753

TwinsUK

AF:

0.0167

AC:

ALSPAC

AF:

0.0148

AC:

ESP6500AA

AF:

0.00363

AC:

ESP6500EA

AF:

0.0144

AC:

124

ExAC

AF:

0.00894

AC:

1086

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.0119

EpiControl

AF:

0.0107

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

OSMR: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.24

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.70

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

REVEL

Benign

0.079

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

0.91

Vest4

0.28

MVP

0.35

MPC

0.25

ClinPred

0.015

GERP RS

-1.3

Varity_R

0.16

gMVP

0.77

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

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