rs34080825

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003999.3(OSMR):c.2876C>G(p.Pro959Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 1,614,034 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P959P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0065 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 175 hom. )

Consequence

OSMR
NM_003999.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.371

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029414892).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00651 (991/152238) while in subpopulation SAS AF = 0.033 (159/4812). AF 95% confidence interval is 0.0289. There are 14 homozygotes in GnomAd4. There are 528 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 991 AD,SD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSMR	NM_003999.3 link	c.2876C>G	p.Pro959Arg	missense_variant	Exon 18 of 18	ENST00000274276.8	NP_003990.1	Q99650-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OSMR	ENST00000274276.8 link	c.2876C>G	p.Pro959Arg	missense_variant	Exon 18 of 18	1	NM_003999.3	ENSP00000274276.3	Q99650-1
OSMR	ENST00000508882.1 link	n.72+845C>G		intron_variant	Intron 1 of 2	3		ENSP00000422372.1	H0Y8W9
OSMR	ENST00000509237.5 link	n.153+845C>G		intron_variant	Intron 2 of 3	5		ENSP00000426729.1	H0YAD1

Frequencies

GnomAD3 genomes

AF:

0.00653

AC:

993

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00923

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0332

Gnomad FIN

AF:

0.00396

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.00700

Gnomad OTH

AF:

0.00956

GnomAD2 exomes

AF:

0.0112

AC:

2815

AN:

251334

AF XY:

0.0133

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00928

Gnomad ASJ exome

AF:

0.0271

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.00766

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.00812

AC:

11867

AN:

1461796

Hom.:

175

Cov.:

AF XY:

0.00948

AC XY:

6893

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.000926

AC:

AN:

33478

American (AMR)

AF:

0.00926

AC:

414

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0258

AC:

675

AN:

26132

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0408

AC:

3519

AN:

86254

European-Finnish (FIN)

AF:

0.00225

AC:

120

AN:

53418

Middle Eastern (MID)

AF:

0.0468

AC:

270

AN:

5768

European-Non Finnish (NFE)

AF:

0.00561

AC:

6238

AN:

1111930

Other (OTH)

AF:

0.00985

AC:

595

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

684

1369

2053

2738

3422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00651

AC:

991

AN:

152238

Hom.:

Cov.:

AF XY:

0.00709

AC XY:

528

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41536

American (AMR)

AF:

0.00915

AC:

140

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0330

AC:

159

AN:

4812

European-Finnish (FIN)

AF:

0.00396

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00700

AC:

476

AN:

68012

Other (OTH)

AF:

0.00946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

137

182

228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00928

Hom.:

Bravo

AF:

0.00643

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.0113

AC:

1368

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.14

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.33

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.37

PrimateAI

Benign

0.23

PROVEAN

Benign

-2.0

REVEL

Benign

0.053

Sift

Benign

0.061

Sift4G

Benign

0.099

Polyphen

0.84

Vest4

0.081

MPC

0.24

ClinPred

0.013

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.14

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

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

rs34080825

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over