Variant rs2278329 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000274276.8(OSMR):c.1657G>A(p.Asp553Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,614,124 control chromosomes in the GnomAD database, including 2,723 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.025 ( 368 hom., cov: 32)

Exomes 𝑓: 0.014 ( 2355 hom. )

Consequence

OSMR
ENST00000274276.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0250

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004065454).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSMR	NM_003999.3 linkuse as main transcript	c.1657G>A	p.Asp553Asn	missense_variant	12/18	ENST00000274276.8	NP_003990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSMR	ENST00000274276.8 linkuse as main transcript	c.1657G>A	p.Asp553Asn	missense_variant	12/18	1	NM_003999.3	ENSP00000274276	P1	Q99650-1

Frequencies

GnomAD3 genomes

AF:

0.0250

AC:

3805

AN:

152150

Hom.:

364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00381

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0329

AC:

8279

AN:

251450

Hom.:

1231

AF XY:

0.0301

AC XY:

4096

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.0346

Gnomad AMR exome

AF:

0.00246

Gnomad ASJ exome

AF:

0.00188

Gnomad EAS exome

AF:

0.363

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.00388

Gnomad NFE exome

AF:

0.00374

Gnomad OTH exome

AF:

0.0166

GnomAD4 exome

AF:

0.0141

AC:

20542

AN:

1461856

Hom.:

2355

Cov.:

AF XY:

0.0137

AC XY:

9942

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0353

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00191

Gnomad4 EAS exome

AF:

0.321

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.00335

Gnomad4 NFE exome

AF:

0.00323

Gnomad4 OTH exome

AF:

0.0274

GnomAD4 genome

AF:

0.0251

AC:

3817

AN:

152268

Hom.:

368

Cov.:

AF XY:

0.0263

AC XY:

1958

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0340

Gnomad4 AMR

AF:

0.00726

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.358

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00381

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0158

Hom.:

585

Bravo

AF:

0.0281

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.0279

AC:

123

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.0330

AC:

4001

Asia WGS

AF:

0.144

AC:

499

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.072

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.94

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.21

REVEL

Benign

0.031

Sift

Benign

0.63

Sift4G

Benign

0.56

Polyphen

0.012

Vest4

0.025

MPC

0.10

ClinPred

0.000040

GERP RS

1.7

Varity_R

0.081

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over