rs10941412

Positions:

• chr5-38919056-G-A
• chr5-38919056-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_003999.3(OSMR):​c.1579G>A​(p.Glu527Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,218 control chromosomes in the GnomAD database, including 24,299 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (2761 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21538 hom.)
• Consequence: OSMR NM_003999.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.74

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004317105).
• BP6: Variant 5-38919056-G-A is Benign according to our data. Variant chr5-38919056-G-A is described in ClinVar as [Benign]. Clinvar id is 3060097.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSMR	NM_003999.3	c.1579G>A	p.Glu527Lys	missense_variant	11/18	ENST00000274276.8	NP_003990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSMR	ENST00000274276.8	c.1579G>A	p.Glu527Lys	missense_variant	11/18	1	NM_003999.3	ENSP00000274276.3
OSMR	ENST00000513831.1	c.400G>A	p.Glu134Lys	missense_variant	3/4	3		ENSP00000423913.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27773 AN: 151966 Hom.: 2755 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.166

GnomAD3 exomes AF: 0.151 AC: 37981 AN: 251098 Hom.: 3293 AF XY: 0.152 AC XY: 20680 AN XY: 135700

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.0936

Gnomad ASJ exome AF: 0.163

Gnomad EAS exome AF: 0.000762

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.172

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.167 AC: 244015 AN: 1461134 Hom.: 21538 Cov.: 33 AF XY: 0.167 AC XY: 121245 AN XY: 726888

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.0998

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.183 AC: 27801 AN: 152084 Hom.: 2761 Cov.: 32 AF XY: 0.183 AC XY: 13583 AN XY: 74350

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.164

Alfa AF: 0.164 Hom.: 4680

Bravo AF: 0.179

TwinsUK AF: 0.175 AC: 650

ALSPAC AF: 0.176 AC: 678

ESP6500AA AF: 0.240 AC: 1058

ESP6500EA AF: 0.168 AC: 1444

ExAC AF: 0.154 AC: 18720

Asia WGS AF: 0.0700 AC: 244 AN: 3478

EpiCase AF: 0.167

EpiControl AF: 0.165

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

OSMR-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 07, 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
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.84	T;T
MetaRNN	Benign	0.0043	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.079
Sift	Benign	0.35	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.98	D;.
Vest4		0.050
MPC		0.24
ClinPred		0.016	T
GERP RS		4.0
Varity_R		0.12
gMVP		0.26

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

Other links and lift over

dbSNP: rs10941412; hg19: chr5-38919158;