Variant rs3749737 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003999.3(OSMR):c.2806C>T(p.Pro936Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00602 in 1,614,130 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.018 ( 52 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 147 hom. )

Consequence

OSMR
NM_003999.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.408

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=0.0022120774).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0177 (2701/152286) while in subpopulation AFR AF= 0.0494 (2054/41558). AF 95% confidence interval is 0.0476. There are 52 homozygotes in gnomad4. There are 1375 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 52 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSMR	NM_003999.3 linkuse as main transcript	c.2806C>T	p.Pro936Ser	missense_variant	18/18	ENST00000274276.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSMR	ENST00000274276.8 linkuse as main transcript	c.2806C>T	p.Pro936Ser	missense_variant	18/18	1	NM_003999.3	P1	Q99650-1
OSMR	ENST00000508882.1 linkuse as main transcript	c.74+775C>T		intron_variant, NMD_transcript_variant		3
OSMR	ENST00000509237.5 linkuse as main transcript	c.155+775C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2700

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0483

Gnomad SAS

AF:

0.0274

Gnomad FIN

AF:

0.00820

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0110

AC:

2758

AN:

251360

Hom.:

AF XY:

0.0105

AC XY:

1430

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0486

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0427

Gnomad SAS exome

AF:

0.0234

Gnomad FIN exome

AF:

0.00953

Gnomad NFE exome

AF:

0.000906

Gnomad OTH exome

AF:

0.00914

GnomAD4 exome

AF:

0.00480

AC:

7013

AN:

1461844

Hom.:

147

Cov.:

AF XY:

0.00516

AC XY:

3750

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0505

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0460

Gnomad4 SAS exome

AF:

0.0230

Gnomad4 FIN exome

AF:

0.00874

Gnomad4 NFE exome

AF:

0.000318

Gnomad4 OTH exome

AF:

0.00873

GnomAD4 genome

AF:

0.0177

AC:

2701

AN:

152286

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1375

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0494

Gnomad4 AMR

AF:

0.00615

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0482

Gnomad4 SAS

AF:

0.0272

Gnomad4 FIN

AF:

0.00820

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.0187

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0438

AC:

193

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.0123

AC:

1494

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000533

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.63

Cadd

Benign

3.6

Dann

Benign

0.71

DEOGEN2

Benign

0.11

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.7

REVEL

Benign

0.040

Sift

Benign

0.12

Sift4G

Benign

0.12

Polyphen

0.39

Vest4

0.060

MPC

0.19

ClinPred

0.0069

GERP RS

3.8

Varity_R

0.034

gMVP

0.32

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

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