rs10941412

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003999.3(OSMR):c.1579G>A(p.Glu527Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,218 control chromosomes in the GnomAD database, including 24,299 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E527A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.18 ( 2761 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21538 hom. )

Consequence

OSMR
NM_003999.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.74

Publications

27 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004317105).

BP6

Variant 5-38919056-G-A is Benign according to our data. Variant chr5-38919056-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060097.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSMR	NM_003999.3 link	c.1579G>A	p.Glu527Lys	missense_variant	Exon 11 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.1579G>A	p.Glu527Lys	missense_variant	Exon 11 of 18	1	NM_003999.3	ENSP00000274276.3		Q99650-1
OSMR	ENST00000513831.1 link	c.400G>A	p.Glu134Lys	missense_variant	Exon 3 of 4	3		ENSP00000423913.1		H0Y9E3

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27773

AN:

151966

Hom.:

2755

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.166

GnomAD2 exomes

AF:

0.151

AC:

37981

AN:

251098

AF XY:

0.152

show subpopulations

Gnomad AFR exome

AF:

0.251

Gnomad AMR exome

AF:

0.0936

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.000762

Gnomad FIN exome

AF:

0.191

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.156

GnomAD4 exome

AF:

0.167

AC:

244015

AN:

1461134

Hom.:

21538

Cov.:

AF XY:

0.167

AC XY:

121245

AN XY:

726888

show subpopulations

African (AFR)

AF:

0.250

AC:

8376

AN:

33464

American (AMR)

AF:

0.0998

AC:

4462

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

4066

AN:

26130

East Asian (EAS)

AF:

0.000403

AC:

AN:

39692

South Asian (SAS)

AF:

0.144

AC:

12403

AN:

86230

European-Finnish (FIN)

AF:

0.189

AC:

10088

AN:

53408

Middle Eastern (MID)

AF:

0.144

AC:

832

AN:

5768

European-Non Finnish (NFE)

AF:

0.174

AC:

193822

AN:

1111346

Other (OTH)

AF:

0.165

AC:

9950

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

9758

19515

29273

39030

48788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6724

13448

20172

26896

33620

<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:

0.183

AC:

27801

AN:

152084

Hom.:

2761

Cov.:

AF XY:

0.183

AC XY:

13583

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.247

AC:

10240

AN:

41456

American (AMR)

AF:

0.132

AC:

2012

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

543

AN:

3468

East Asian (EAS)

AF:

0.00135

AC:

AN:

5182

South Asian (SAS)

AF:

0.148

AC:

713

AN:

4820

European-Finnish (FIN)

AF:

0.194

AC:

2057

AN:

10586

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.172

AC:

11697

AN:

67968

Other (OTH)

AF:

0.164

AC:

346

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1176

2351

3527

4702

5878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.170

Hom.:

7531

Bravo

AF:

0.179

TwinsUK

AF:

0.175

AC:

650

ALSPAC

AF:

0.176

AC:

678

ESP6500AA

AF:

0.240

AC:

1058

ESP6500EA

AF:

0.168

AC:

1444

ExAC

AF:

0.154

AC:

18720

Asia WGS

AF:

0.0700

AC:

244

AN:

3478

EpiCase

AF:

0.167

EpiControl

AF:

0.165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

OSMR-related disorder

Benign:1

Nov 07, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.84

T;T

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

PhyloP100

2.7

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.079

Sift

Benign

0.35

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.98

D;.

Vest4

0.050

MPC

0.24

ClinPred

0.016

GERP RS

4.0

Varity_R

0.12

gMVP

0.26

Mutation Taster

=99/1

polymorphism (auto)

(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