rs2289926

chr5-38925355-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003999.3(OSMR):c.2196G>A(p.Thr732=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,613,836 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (123 hom.)
• Consequence: OSMR NM_003999.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-38925355-G-A is Benign according to our data. Variant chr5-38925355-G-A is described in ClinVar as [Benign]. Clinvar id is 779884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSMR	NM_003999.3	c.2196G>A	p.Thr732=	synonymous_variant	15/18	ENST00000274276.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSMR	ENST00000274276.8	c.2196G>A	p.Thr732=	synonymous_variant	15/18	1	NM_003999.3	P1

Frequencies

GnomAD3 genomes AF: 0.00340 AC: 517 AN: 152118 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0785

Gnomad SAS AF: 0.00519

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00611 AC: 1536 AN: 251350 Hom.: 61 AF XY: 0.00560 AC XY: 760 AN XY: 135826

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.0779

Gnomad SAS exome AF: 0.00144

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00229 AC: 3341 AN: 1461600 Hom.: 123 Cov.: 32 AF XY: 0.00225 AC XY: 1635 AN XY: 727144

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.0692

Gnomad4 SAS exome AF: 0.00155

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000306

Gnomad4 OTH exome AF: 0.00603

GnomAD4 genome AF: 0.00339 AC: 516 AN: 152236 Hom.: 13 Cov.: 32 AF XY: 0.00360 AC XY: 268 AN XY: 74416

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0785

Gnomad4 SAS AF: 0.00519

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.000881 Hom.: 1

Bravo AF: 0.00347

Asia WGS AF: 0.0340 AC: 117 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.90
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2289926; hg19: chr5-38925457;