chr5-38883969-T-G

Variant names:

Variant summary

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

The NM_003999.3(OSMR):c.561T>G(p.His187Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0775 in 1,613,524 control chromosomes in the GnomAD database, including 5,554 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.096 ( 795 hom., cov: 33)

Exomes 𝑓: 0.076 ( 4759 hom. )

Consequence

OSMR
NM_003999.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.69

Publications

23 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=0.0012784004).

BP6

Variant 5-38883969-T-G is Benign according to our data. Variant chr5-38883969-T-G is described in ClinVar as [Benign]. Clinvar id is 3038218.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSMR	NM_003999.3 link	c.561T>G	p.His187Gln	missense_variant	Exon 5 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.561T>G	p.His187Gln	missense_variant	Exon 5 of 18	1	NM_003999.3	ENSP00000274276.3		Q99650-1
OSMR	ENST00000502536.5 link	c.561T>G	p.His187Gln	missense_variant	Exon 5 of 7	1		ENSP00000422023.1		Q99650-2

Frequencies

GnomAD3 genomes

AF:

0.0958

AC:

14575

AN:

152142

Hom.:

786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0643

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.0306

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0739

Gnomad OTH

AF:

0.0974

GnomAD2 exomes

AF:

0.0830

AC:

20842

AN:

251258

AF XY:

0.0851

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0476

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.0323

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.0738

Gnomad OTH exome

AF:

0.0873

GnomAD4 exome

AF:

0.0756

AC:

110424

AN:

1461264

Hom.:

4759

Cov.:

AF XY:

0.0772

AC XY:

56155

AN XY:

726964

show subpopulations

African (AFR)

AF:

0.149

AC:

4993

AN:

33454

American (AMR)

AF:

0.0511

AC:

2286

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

4297

AN:

26130

East Asian (EAS)

AF:

0.0304

AC:

1205

AN:

39682

South Asian (SAS)

AF:

0.116

AC:

9971

AN:

86234

European-Finnish (FIN)

AF:

0.0994

AC:

5311

AN:

53420

Middle Eastern (MID)

AF:

0.138

AC:

795

AN:

5768

European-Non Finnish (NFE)

AF:

0.0688

AC:

76423

AN:

1111478

Other (OTH)

AF:

0.0852

AC:

5143

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

5301

10602

15903

21204

26505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2858

5716

8574

11432

14290

<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:

0.0959

AC:

14607

AN:

152260

Hom.:

795

Cov.:

AF XY:

0.0971

AC XY:

7233

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.140

AC:

5797

AN:

41528

American (AMR)

AF:

0.0641

AC:

982

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

567

AN:

3470

East Asian (EAS)

AF:

0.0305

AC:

158

AN:

5178

South Asian (SAS)

AF:

0.125

AC:

601

AN:

4826

European-Finnish (FIN)

AF:

0.106

AC:

1128

AN:

10608

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0739

AC:

5025

AN:

68018

Other (OTH)

AF:

0.102

AC:

216

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

685

1370

2055

2740

3425

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<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:

0.0830

Hom.:

1978

Bravo

AF:

0.0952

TwinsUK

AF:

0.0682

AC:

253

ALSPAC

AF:

0.0669

AC:

258

ESP6500AA

AF:

0.145

AC:

637

ESP6500EA

AF:

0.0749

AC:

644

ExAC

AF:

0.0837

AC:

10165

Asia WGS

AF:

0.119

AC:

412

AN:

3478

EpiCase

AF:

0.0768

EpiControl

AF:

0.0763

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

OSMR-related disorder

Benign:1

Nov 15, 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

0.10

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.096

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.37

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

PhyloP100

-2.7

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.015

Sift

Benign

0.33

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.010

B;B

Vest4

0.066

MutPred

0.24

Gain of disorder (P = 0.154);Gain of disorder (P = 0.154);

MPC

0.086

ClinPred

0.0018

GERP RS

-8.3

Varity_R

0.047

gMVP

0.30

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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