chr5-38903980-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/21 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

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

amyloidosis, primary localized cutaneous, 1
Inheritance: SD, AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
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 -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 VariationId is 791577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1293 AD,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

GnomAD2 exomes

AF:

0.00868

AC:

2180

AN:

251192

AF XY:

0.00877

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 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

African (AFR)

AF:

0.00206

AC:

AN:

33476

American (AMR)

AF:

0.00315

AC:

141

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000230

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00226

AC:

195

AN:

86240

European-Finnish (FIN)

AF:

0.0174

AC:

928

AN:

53418

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0147

AC:

16363

AN:

1111920

Other (OTH)

AF:

0.0107

AC:

645

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

958

1917

2875

3834

4792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.00849

AC:

1293

AN:

152306

Hom.:

Cov.:

AF XY:

0.00838

AC XY:

624

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00262

AC:

109

AN:

41568

American (AMR)

AF:

0.00438

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0148

AC:

157

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0138

AC:

939

AN:

68022

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

137

206

274

343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0117

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

- -

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 -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

-0.029

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

PromoterAI

0.022

Neutral

(source)

Varity_R

0.16

gMVP

0.77

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over