rs34080825

chr5-38933380-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003999.3(OSMR):c.2876C>G(p.Pro959Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00797 in 1,614,034 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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. Synonymous variant affecting the same amino acid position (i.e. P959P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0065 (14 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (175 hom.)
• Consequence: OSMR NM_003999.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029414892).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00651 (991/152238) while in subpopulation SAS AF= 0.033 (159/4812). AF 95% confidence interval is 0.0289. There are 14 homozygotes in gnomad4. There are 528 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 14 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSMR	NM_003999.3	c.2876C>G	p.Pro959Arg	missense_variant	18/18	ENST00000274276.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSMR	ENST00000274276.8	c.2876C>G	p.Pro959Arg	missense_variant	18/18	1	NM_003999.3	P1
OSMR	ENST00000508882.1	c.74+845C>G		intron_variant, NMD_transcript_variant		3
OSMR	ENST00000509237.5	c.155+845C>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00653 AC: 993 AN: 152120 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00923

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00700

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.0112 AC: 2815 AN: 251334 Hom.: 62 AF XY: 0.0133 AC XY: 1812 AN XY: 135836

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00928

Gnomad ASJ exome AF: 0.0271

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0382

Gnomad FIN exome AF: 0.00268

Gnomad NFE exome AF: 0.00766

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.00812 AC: 11867 AN: 1461796 Hom.: 175 Cov.: 33 AF XY: 0.00948 AC XY: 6893 AN XY: 727210

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.00926

Gnomad4 ASJ exome AF: 0.0258

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0408

Gnomad4 FIN exome AF: 0.00225

Gnomad4 NFE exome AF: 0.00561

Gnomad4 OTH exome AF: 0.00985

GnomAD4 genome AF: 0.00651 AC: 991 AN: 152238 Hom.: 14 Cov.: 32 AF XY: 0.00709 AC XY: 528 AN XY: 74428

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00915

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0330

Gnomad4 FIN AF: 0.00396

Gnomad4 NFE AF: 0.00700

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00928 Hom.: 2

Bravo AF: 0.00643

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00721 AC: 62

ExAC AF: 0.0113 AC: 1368

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0107

EpiControl AF: 0.0100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	13
Dann	Benign	0.94
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.053
Sift	Benign	0.061	T
Sift4G	Benign	0.099	T
Polyphen		0.84	P
Vest4		0.081
MPC		0.24
ClinPred		0.013	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.040
gMVP		0.14

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: rs34080825; hg19: chr5-38933482;