rs2278329

Variant names:

• chr5-38921686-G-A
• rs2278329
• NM_003999.3:c.1657G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003999.3(OSMR):​c.1657G>A​(p.Asp553Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,614,124 control chromosomes in the GnomAD database, including 2,723 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.025 (368 hom., cov: 32)
  • Exomes 𝑓: 0.014 (2355 hom.)
• Consequence: OSMR NM_003999.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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=0.004065454).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSMR	NM_003999.3	c.1657G>A	p.Asp553Asn	missense_variant	Exon 12 of 18	ENST00000274276.8	NP_003990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSMR	ENST00000274276.8	c.1657G>A	p.Asp553Asn	missense_variant	Exon 12 of 18	1	NM_003999.3	ENSP00000274276.3

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3805 AN: 152150 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00727

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0329 AC: 8279 AN: 251450 Hom.: 1231 AF XY: 0.0301 AC XY: 4096 AN XY: 135898

Gnomad AFR exome AF: 0.0346

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00188

Gnomad EAS exome AF: 0.363

Gnomad SAS exome AF: 0.0109

Gnomad FIN exome AF: 0.00388

Gnomad NFE exome AF: 0.00374

Gnomad OTH exome AF: 0.0166

GnomAD4 exome AF: 0.0141 AC: 20542 AN: 1461856 Hom.: 2355 Cov.: 32 AF XY: 0.0137 AC XY: 9942 AN XY: 727232

Gnomad4 AFR exome AF: 0.0353

Gnomad4 AMR exome AF: 0.00273

Gnomad4 ASJ exome AF: 0.00191

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.0114

Gnomad4 FIN exome AF: 0.00335

Gnomad4 NFE exome AF: 0.00323

Gnomad4 OTH exome AF: 0.0274

GnomAD4 genome AF: 0.0251 AC: 3817 AN: 152268 Hom.: 368 Cov.: 32 AF XY: 0.0263 AC XY: 1958 AN XY: 74454

Gnomad4 AFR AF: 0.0340

Gnomad4 AMR AF: 0.00726

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00381

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0158 Hom.: 585

Bravo AF: 0.0281

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.0279 AC: 123

ESP6500EA AF: 0.00291 AC: 25

ExAC AF: 0.0330 AC: 4001

Asia WGS AF: 0.144 AC: 499 AN: 3478

EpiCase AF: 0.00300

EpiControl AF: 0.00373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.73
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.94	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.031
Sift	Benign	0.63	T
Sift4G	Benign	0.56	T
Polyphen		0.012	B
Vest4		0.025
MPC		0.10
ClinPred		0.000040	T
GERP RS		1.7
Varity_R		0.081
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2278329; hg19: chr5-38921788; COSMIC: COSV57082505; COSMIC: COSV57082505;