Variant 5-38876259-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003999.3(OSMR):c.132G>A(p.Thr44=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,613,418 control chromosomes in the GnomAD database, including 272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 132 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 140 hom. )

Consequence

OSMR
NM_003999.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.250

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 5-38876259-G-A is Benign according to our data. Variant chr5-38876259-G-A is described in ClinVar as [Benign]. Clinvar id is 776041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.074 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSMR	NM_003999.3 linkuse as main transcript	c.132G>A	p.Thr44=	synonymous_variant	3/18	ENST00000274276.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSMR	ENST00000274276.8 linkuse as main transcript	c.132G>A	p.Thr44=	synonymous_variant	3/18	1	NM_003999.3	P1	Q99650-1
OSMR	ENST00000502536.5 linkuse as main transcript	c.132G>A	p.Thr44=	synonymous_variant	3/7	1			Q99650-2

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3298

AN:

151840

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0763

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00603

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00600

AC:

1508

AN:

251128

Hom.:

AF XY:

0.00458

AC XY:

621

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.0797

Gnomad AMR exome

AF:

0.00394

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00243

AC:

3556

AN:

1461460

Hom.:

140

Cov.:

AF XY:

0.00208

AC XY:

1512

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.0827

Gnomad4 AMR exome

AF:

0.00463

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.0218

AC:

3306

AN:

151958

Hom.:

132

Cov.:

AF XY:

0.0205

AC XY:

1526

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0762

Gnomad4 AMR

AF:

0.00609

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00608

Hom.:

Bravo

AF:

0.0256

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

OSMR-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 04, 2019

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

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.2

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over