rs2289925

Positions:

• chr5-38925268-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_003999.3(OSMR):​c.2109C>T​(p.Asn703=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,613,822 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0016 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (51 hom.)
• Consequence: OSMR NM_003999.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.258

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-0.258 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00158 (241/152120) while in subpopulation EAS AF= 0.0363 (188/5174). AF 95% confidence interval is 0.0321. There are 7 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 7 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSMR	NM_003999.3	c.2109C>T	p.Asn703=	synonymous_variant	15/18	ENST00000274276.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSMR	ENST00000274276.8	c.2109C>T	p.Asn703=	synonymous_variant	15/18	1	NM_003999.3	P1

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 241 AN: 152004 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.00478

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00295 AC: 741 AN: 251400 Hom.: 10 AF XY: 0.00276 AC XY: 375 AN XY: 135862

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0349

Gnomad SAS exome AF: 0.00160

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.00148 AC: 2168 AN: 1461702 Hom.: 51 Cov.: 32 AF XY: 0.00152 AC XY: 1108 AN XY: 727172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0437

Gnomad4 SAS exome AF: 0.00179

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.00162

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152120 Hom.: 7 Cov.: 32 AF XY: 0.00195 AC XY: 145 AN XY: 74356

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.00478

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000477 Hom.: 0

Bravo AF: 0.00187

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.88
DANN	Benign	0.33

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: rs2289925; hg19: chr5-38925370;